Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases.However,conventional topical drug deliv...Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases.However,conventional topical drug delivery often results in a burst release of the drug,leading to transient retention(inefficacy)and undesirable diffusion(toxicity)in vivo.Therefore,a drug delivery system that responds to changes in the microenvironment of tissue regeneration and controls vascular endothelial growth factor release is crucial to improve the treatment of ischemic stroke.Matrix metalloproteinase-2(MMP-2)is gradually upregulated after cerebral ischemia.Herein,vascular endothelial growth factor mimic peptide QK was self-assembled with MMP-2-cleaved peptide PLGLAG(TIMP)and customizable peptide amphiphilic(PA)molecules to construct nanofiber hydrogel PA-TIMP-QK.PA-TIMP-QK was found to control the delivery of QK by MMP-2 upregulation after cerebral ischemia/reperfusion and had a similar biological activity with vascular endothelial growth factor in vitro.The results indicated that PA-TIMP-QK promoted neuronal survival,restored local blood circulation,reduced blood-brain barrier permeability,and restored motor function.These findings suggest that the self-assembling nanofiber hydrogel PA-TIMP-QK may provide an intelligent drug delivery system that responds to the microenvironment and promotes regeneration and repair after cerebral ischemia/reperfusion injury.展开更多
BACKGROUND： The majority of studies addressing spinal cord ischemia/reperfusion injury （SCIRI） have focused on drugs, proteins, cytokines, and various surgical techniques. A recent study reports that human umbilica...BACKGROUND： The majority of studies addressing spinal cord ischemia/reperfusion injury （SCIRI） have focused on drugs, proteins, cytokines, and various surgical techniques. A recent study reports that human umbilical cord mesenchymal stem cell （hUCMSC） transplantation achieves good therapeutic effects, but the mechanisms underlying nerve protection remain poorly understood. OBJECTIVE： To observe survival of transplanted hUCMSCs in SCIRI rat models and the influence on motor function in the hind limbs, to determine interleukin-8 expression and cellular apoptosis in spinal cord tissues, and to verify the hypothesis that hUCMSC transplantation exhibits protective effects on SCIRI. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Laboratory of the Department of Orthopedics in the First Affiliated Hospital of Soochow University, China between January 2007 and December 2008. MATERIALS： hUCMSCs were harvested from umbilical cord blood of healthy pregnant women after parturition in the Obstetrical Department of the First Affiliated Hospital of Soochow University, China. Rabbit anti-human BrdU monoclonal antibody was provided by DAKO, USA. Terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） Kit and enzyme-linked immunosorbent assay （ELISA） Kit were purchased by Wuhan Boster, China. METHODS： A total of 72 healthy, Wistar, adult rats were randomly assigned to three groups： sham-surgery, model, and transplantation, with 24 rats in each group. SCIRI was induced in the model and transplantation groups via the abdominal aorta block method. The infrarenal abdominal aorta was not blocked in the sham-surgery group. Prior to abdominal aorta occlusion, 0.2 03 mL bromodeoxyuridine （BrdU）-Iabeled hUCMSCs suspension （cell concentration 5 × 10 3/uL） was injected through the great saphenous vein of the hind limb, and an equal volume of physiological saline was administered to the model and sham-surgery groups. MAIN OUTCOME MEASURES： Pathological observation of rat spinal cord tissues was performed by hematoxylin-eosin staining at 6, 24, and 48 hours post-surgery. Immunohistochemistry was applied to determine hUCMSCs survival in the spinal cord. The amount of cellular apoptosis and interleukin-8 expression in spinal cord tissues was assayed utilizing the TUNEL and ELISA methods, respectively. Motor function in the hind limbs was evaluated according to Jacob＇s score. RESULTS： Numerous BrdU-positive cells were observed in spinal cord tissues from the transplantation group. The number of apoptotic cells and interleukin-8 levels significantly decreased in the transplantation group （P 〈 0.05）, pathological injury was significantly ameliorated, and motor function scores significantly increased （P 〈 0.05） compared with the model group. CONCLUSION： Via vein transplantation, hUCMSCs were shown to reach and survive in the injury area. Results suggested that the transplanted hUCMSCs contributed to significantly improved pathological changes in the injured spinal cord, as well as motor function, following SCIRI. The protective mechanism correlated with inhibition of cellular apoptosis and reduced production of inflammatory mediators.展开更多
BACKGROUND: The fluidity of cell membrane can be affected by various factors. Many experiments have confirmed that the ischemia/reperfusion of organic tissue can increase the contents of free radicals, which lead to h...BACKGROUND: The fluidity of cell membrane can be affected by various factors. Many experiments have confirmed that the ischemia/reperfusion of organic tissue can increase the contents of free radicals, which lead to high rigidity and low fluidity of cell membrane, and the conditions can be changed by Chuanxiongqin. OBJECTIVE: To observe the effect and mechanism of Chuanxiongqin hydrochloride on the fluidity of brain cell membrane in rat models of ischemia/reperfusion. DESIGN: A completely randomized controlled animal trial. SETTINGS: Institute of Brain Sciences; Department of Physiology, Medical College, Datong University. MATERIALS: Twenty male grade Ⅰ Wistar rats of 170-220 g were randomly divided into model group (n =10) and control group (n =10). Chuanxiongqin hydrochloride (molecular mass was 172.2) was purchased from the National Institute for the Control of Pharmaceutical and Biological Products (batch number: 0817-9803); Spin labelers: 5-doxyl-stearlic acid methylester (5DS), 16-doxyl-stearlic acid methylester (16DS), xanthine, xanthine oxidase (XOD) and 5,5-dimeth-1-pyrroline- N-oxide (DMPO) from Sigma Company; Bruker ESP 300 electron paramagnetic resonance (EPR) spectrometer by Bruker Company (Germany). METHODS: The experiments were carried out in the State Key Laboratory of Natural and Biomimetic Drugs, Peking University from June 2001 to July 2002. In the model group, rats were made into models of cerebral ischemia by 30-minute ligation and 2-hour reperfusion of common carotid arteries; The rats in the control group were not made into models. The order parameter (S) and rotational correlation time (τc) were detected with the ESR spectrometer by means of spin labeling. The greater the S and τc, the smaller the fluidity. Meanwhile, the clearance rate of free radicals was detected with ESR spin trapping. The measurement data were compared using the t test. MAIN OUTCOME MEASURES: The S, τc and clearance rates of O2 · and OH· free radicals were compared between the model group and control group. RESULTS: The S and τc in the model group [0.738 4±0.003 5; (8.472±0.027)×10-10 s/circle] were obviously different from those in the control group [0.683 9±0.008 3; (7.945±0.082)×10-10 s/circle, t =5.731, 5.918, P < 0.05], which suggested that ischemia/reperfusion injury decreased the fluidity of brain cell membrane. After adding Chuanxiongqin hydrochloride, there were no obvious differences between the model group [0.688 5±0.030 5; (7.886±0.341)×10-10 s/circle] and control group (P > 0.05), indicating that Chuanxiongqin hydrochloride could recover the fluidity of brain cell membrane after ischemia/reperfusion injury close to the level in the normal control group. Chuanxiongqin hydrochloride could directly scavenge the O2 · and OH· free radicals, and the maximal clearance rates were 83.92% and 44.99% respectively. CONCLUSION: Chuanxiongqin hydrochloride increases the fluidity of membrane of ischemia-injured brain cell by scavenging both O2 ·and OH· free radicals.展开更多
Current antiplatelet drugs mainly focus on prevention rather than the more clinically relevant issue of clearance of an existing thrombus. We recently described a novel and effective therapeutic strategy for dissoluti...Current antiplatelet drugs mainly focus on prevention rather than the more clinically relevant issue of clearance of an existing thrombus. We recently described a novel and effective therapeutic strategy for dissolution of preexisting platelet thrombus in a murine ischemic stroke model with a bifunctional platelet GPIIIa49-66 ligand (Single-chain antibody Linked first Kringle 1 of plasminogen, named SLK), which homes to newly deposited fibrin strands tangled of platelet thrombus and induces aggregated platelet fragmentation. In this study, we perform in-depth analysis of the effect of SLK on myocardial ischemia-reperfusion (IR) injury in rats. We show that SLK dose-dependently reduces lactate dehydrogenase (LDH) release as well as mean infarction size of left ventricle. Histological observation demonstrates that the arterial thrombi in coronary arteries of rat almost disappear after SLK injection. Optimal dose of SLK (37.5 μg/ individual) provides the myocardial protection at 2 hours post-infusion. However, there are no significant protective effects if SLK was given at 4 or 8 hours post-infusion. The combined application of SLK and urokinase (UK) demonstrates greater myocardial protection than UK alone at 2 hours post-infusion. Thus, SLK could be used as a thrombolytic alternative in other arterial vascular beds associated with thrombosis to enhance fibrinolysis.展开更多
Aim Salvia miltiorrhiza Bunge （SM） and lignum dalbergiae odoriferae （DO） are both traditional Chi- nese medicine that have cardioprotective effects. Here, we further examined the combined effects of SM and DO on r...Aim Salvia miltiorrhiza Bunge （SM） and lignum dalbergiae odoriferae （DO） are both traditional Chi- nese medicine that have cardioprotective effects. Here, we further examined the combined effects of SM and DO on rat myocardial ischemia/reperfusion injury. The possible mechanism of SM and DO also were elucidated. Methods DO was divided into aqueous extract of lignum dalbergiae odoriferae （DOW） and lignum dalbergiae odoriferae oil （DOO）. Sprague-Dawley rats were randomized to seven groups： sham group, model group, treatment groups inclu- ding SM （10 g · kg^-1）, DOW （5 g · kg^-1）, DOO （0.5 ml · kg^-1）, SM ＋ DOW （10 g · kg^-1 ＋ 5 g · kg^-1）, SM ＋ DOO （ 10 g · kg^-1 ＋ 0. 5 ml · kg^-1）. Rats were pretreated with homologous drug for 7 days and then subjec- ted to 30 rain of ischemia followed by 180 rain of reperfusion. Electrocardiogram （ECG） and heart rate were moni- tored and recorded continuously. At the end of reperfusion, blood samples were collected to determine the serum levels of creatine kinase-MB （CK-MB） and lactate dehydrogenase （LDH）. Hearts were harvested to assess heart- body rate, infarct size and histopathological changes as well. Maximum and minimum effective points were deter- mined by measuring indicators associate with myocardial injury at different time-points of reperfusion （Smin, 15min, 30min, 45rain, 60min, 120min, 180min）. The potential therapeutic mechanism of SM and SM ＋ DOO were carried out by detecting superoxide dismutase （SOD）, malondialdehyde （MDA）, tumor necrosis factor-alpha （TNF-alpha） and interleukin 6 （IL-6）. Results The results showed SM and DO can ameliorate cardiac function respectively, and this cardioprotective effect was further strengthened by their combinations. Among all the combi- nations, SM ＋ DOO showed predominant potential to improve ECG and heart rate, reduce heart-body rate （28.5% ＋ 1.4% , P 〈 0.01 vs model） and myocardial infarct size （ 20.96% ＋ 1.61% , P 〈 0.01 vs model, P 〈 0.05 vs SM） , attenuate histopathological damage, decrease the levels of CK-MB and LDH （P 〈 0.01 vs model, P 〈 0.05 vs SM）. The maximum effective points of SM and SM ＋ DOO were 15min and 30rain respectively, and the minimum effective points of them were 180rain. In reducing serum level of MDA, TNF-alpha, IL-6 and increasing SOD activ- ity, SM ＋ DOO was similar to SM. Conclusion The results of this study indicated that SM ＋ DOO have combined effects that are highly effective than single pretreatment against myocardial ischemie reperfusion injury in rats. The possible mechanism of SM and DO were likely through its anti-oxidant and anti-inflammatory properties, and thus may be an effective and promising medicine for both prophylaxis and treatment of ischemic heart disease.展开更多
Objective To study the protecting effects and mechanism of betaine hydrochloride on hepatic ischemia-reperfusion injury in rats.Methods Fourty SD rats were randomly divided into 5 groups(8 animals in each group):sham-...Objective To study the protecting effects and mechanism of betaine hydrochloride on hepatic ischemia-reperfusion injury in rats.Methods Fourty SD rats were randomly divided into 5 groups(8 animals in each group):sham-operated control group(A),hepatic ischemia-reperfusion group(B),200 mg·kg-1 400 mg·kg-1 800 mg·kg-1 betaine hydrochloride+hepatic ischemia-reperfusion group(C、D、E).betaine hydrochloride was administered to animals byoral route in group C、D、E for 7 days before ischemia.A、B group was administered with NS.Made the animal model of part hepatic ischemia-reperfusion.Serum alanine aminotransferase(ALT),aspartate aminotransferase(AST)levels in the blood and themalondialdehyde(MDA),superoxide dismutase(SOD),protein content in hepatic tissue were determined after the liver had been reperfused for 24 hours;the hepatic tissue was examined under lightmicroscope and the cell apoptosis was demonstrated with flow cytometry.Results ALT,AST,MDA increased and SOD decreased significantly in B group when compared those in the A group(P<0.05),Hepatic apoptosis was significantly increased;ALT,AST,MDA decreased and SOD increased significantly in betaine hydrochloride 200 mg·kg-1(C)group when compared those in the B group(P<0.05).Hepatic apoptosis was significantly lower,The histologic changes of the liver tissue under lightmicroscope in the C group was more easer than in the I/R group(B).Conclusions Betaine hydrochloride has the ability to scavenge oxygen free radical(OFR),reduce lipid peroxidation and inhibition of apoptosis.So it can protect the rats liver damaged by ischemia-reperfusion.展开更多
BACKGROUND ： The application of exogenous antioxidant is always the focus in the prevention and treatment of cerebral ischemia. Phycocyanin has the effects against oxidation and inflammation, but its role in the path...BACKGROUND ： The application of exogenous antioxidant is always the focus in the prevention and treatment of cerebral ischemia. Phycocyanin has the effects against oxidation and inflammation, but its role in the pathophysiological process of cerebral ischemia reperfusion injury still needs further investigation. OBJECTIVE： To observe the effects of phycocyanin on the expression of superoxide dismutase （SOD） apoptosis and form of the nerve cells in rats after cerebral ischemia reperfusion injury. DESIGN： A randomized control animal experiment SETTING ： Institute of Cerebrovascular Disease, Medical School Hospital of Qingdao University MATERIALS： Fifty-two healthy adult male Wistar rats of clean degree, weighing 220-260 g, were used. Phycocyanin was provided by the Institute of Oceanology, Chinese Academy of Sciences. METHODS： The experiments were carried out in Shangdong Key Laboratory for Prevention and Treatment of Brain Diseases from May to December 2005. ① All the rats were divided into three groups according to the method of random number table： sham-operated group （n=4）, control group （n=24） and treatment group （n=24）. Models of middle cerebral artery occlusion/reperfusion （MCAO/R） were established by the introduction of thread through external and internal carotid arteries in the control group and treatment group. After 1-hour ischemia and 2-hour reperfusion, rats in the treatment group were administrated with gastric perfusion of phy- cocyanin suspension （0.1 mg/g）, and those in the control group were given saline of the same volume, and no treatment was given to the rats in the sham-operated group. ②The samples were removed and observed at ischemia for 1 hour and reperfusion for 6 and 12 hours and 1, 3, 7 and 14 days respectively in the control group and treatment group, 4 rats for each time point, and those were removed at 1 day postoperatively in the sham-operated group. Forms of the nerve cells were observed with toluidine blue staining. Apoptosis after cerebral ischemia reperfusion was detected with TUNEL technique. SOD expression was detected with immunohistochemical technique.③ The intergroup difference was compared with the ttest. MAIN OUTCOME MEASURES： The apoptosis of the nerve cells and SOD expression were mainly observed in each group. RESULTS： Finally, 52 rats were involved in the analysis of results. ① Number of apoptotic cells： In the sham-operated group, a few apoptotic cells could be observed in brain tissue. The apoptotic cells at each time point in the control group and treatment group were obviously more than those in the sham-operated group （P 〈 0.05）. In the treatment group, the numbers of apoptotic cells at 12 hours, 1 and 3 days after reperfusion were significantly fewer than those in the control group, and those at 6 hours, 7 and 14 days were similar to those in the control group. ② Number of SOD positive cells： In the sham-operated group, there was weak expression of SOD in brain tissue, and the positive cells were extremely few, the positive cells at each time point were significantly more in the control group and treatment group than in the sham-operated group （P 〈 0.05）. In the treatment group, the numbers of positive cells at 6 and 12 hours, 1 and 3 days after reperfusion were significantly fewer than those in the control group, and those at 7-14 days were similar to those in the control group. ③ Cellular forms： In the control group, the karyopyknosis occurred in the nerve cells, which were irregularly distributed, nucleolus disappeared, and some scattered cell fragments were observed. The forms of the nerve cells in the treatment group were generally normal. CONCLUSION ： Phycocyanin plays a neuroprotective role in cerebral ischemia reperfusion injury by activating the SOD expression and inhibiting apoptosis.展开更多
Oxidative stress occurs in the organism with ischemia due to tourniquet use and subsequent reperfusion. Oxidative stress increases postoperative morbidity. Some Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) perform t...Oxidative stress occurs in the organism with ischemia due to tourniquet use and subsequent reperfusion. Oxidative stress increases postoperative morbidity. Some Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) perform their anti-inflammatory effects in part by binding or inhibiting their formation of active oxygen radicals at the site of inflammation. In this study, we aimed to evaluate the effect of IV ibuprofen on ischemia-reperfusion injury (IRI) in patients undergoing total knee arthroplasty over oxidative stress parameters.<span> </span><span>The patients were randomly divided into two groups. Each patient</span><span>’</span><span>s protocol number, age, sex, body mass index (BMI), additional disease, drug use, tourniquet time, hemoglobin value, additional analgesic requirement and application, adverse reaction development on the first postoperative day were recorded in the research follow-up form. Both groups of patients;before anesthesia, 45 minutes after tourniquet application, 5 minutes after tourniquet lowering, 20 minutes after tourniquet lowering and at 24th-hour post-op;TOS, TAS, paraoxonase, arylesterase, myeloperoxidase, catalase, ceruloplasmin, albumin, IMA, thiol-disulfide balance tests were studied. Statistical analysis of test results was performed.</span><span> </span><span>We observed that antioxidants decreased and oxidants increased on the first postoperative day in both groups in patients who underwent total knee arthroplasty. The decrease in antioxidant parameters was higher in IV ibuprofen doses compared to the control group in the case group;these doses indicate that the drug adversely affects the organism in the fight against oxidative stress, which is an undesirable effect. To evaluate this negative effect of IV ibuprofen which is increasingly used in postoperative analgesia, studies with different doses of drugs and different surgeries may be needed.</span>展开更多
Transient receptor potential(TRP)channels are a type of cation channel located on the cell membrane.TRP channels are divided into 7 subfamilies(TRPC,TRPA,TRPM,TRPV,TRPN,TRPP and TRPML)and widely expressed in myocardia...Transient receptor potential(TRP)channels are a type of cation channel located on the cell membrane.TRP channels are divided into 7 subfamilies(TRPC,TRPA,TRPM,TRPV,TRPN,TRPP and TRPML)and widely expressed in myocardial tissue.In recent years,with the application of gene knockout and transgenic model animals,it has been found that members of the TRP channel subfamilies TRPM,TRPC and TRPV are closely related to myocardial ischemia-reperfusion injury.The activation or inhibition of TRP channels participates in the regulation of myocardial ischemia-reperfusion injury,reduces the infarct area of the myocardium,and exerts a protective effect.Therefore,this paper first summarizes the structural characteristics of TRPM,TRPC,and TRPV and their distribution in the cardiovascular system,and then summarizes the mechanisms of TRPM,TRPC,and TRPV that regulate myocardial ischemia and reperfusion,which will provide a certain theoretical basis for treatment of myocardial ischemia-reperfusion injury.展开更多
BACKGROUND: Calcitonin gene-related peptide (CGRP) and nerve growth actor (NGF) cam improve spatial learning and memory abilities of rats with cerebral ischemia/reperfusion; however, the effect of combination of them ...BACKGROUND: Calcitonin gene-related peptide (CGRP) and nerve growth actor (NGF) cam improve spatial learning and memory abilities of rats with cerebral ischemia/reperfusion; however, the effect of combination of them on relieving learning and memory injury following cerebral ischemia/reperfusion should be further studied. OBJECTIVE: To study the effects of exogenous CGRP and NGF on learning and memory abilities of rats with focal cerebral ischemia/reperfusion. DESIGN: Randomized controlled animal study. SETTING: Department of Neurosurgery, the Second Hospital of Xiamen; Department of Neurosurgery, the Second Affiliated Hospital of China Medical University; Department of Neurobiology, Basic Medical College of China Medical University. MATERIALS: A total of 30 healthy male SD rats, aged 8 weeks, of clean grade, weighing 250-300 g, were provided by Experimental Animal Department of China Medical University. All rats were randomly divided into sham-operation group, ischemia/reperfusion group and treatment group with 10 in each group. The main reagents were detailed as the follows: 100 g/L chloral hydrate, 0.5 mL CGRP (2 mg/L, Sigma Company, USA), and NGF (1× 106 U/L, 0.5 mL, Siweite Company, Dalian). METHODS: The experiment was carried out in the Department of Neurobiology, Basic Medical College of China Medical University from February to July 2005. Rat models of middle cerebral artery occlusion were established by method of occlusion, 2 hours after that rats were anesthetized and the thread was slightly drawn out for 10 mm under direct staring to perform reperfusion. Rats in the ischemia/reperfusion group received intraperitoneal injection of 1 mL saline via the abdomen at two hours later, while rats in the treatment group at 2 hours later received intraperitoneal injection of 2 mg/L CGRP (0.5 mL) and 1×106 U/L NGF (0.5 mL) once a day for 10 successive days. First administration was accomplished within 15 minutes after ischemia/reperfusion. Rats in the sham-operation group were separated of the vessels without occlusion or administration. The neural function was evaluated with Zea Longa 5-grade scale. Animals with the score of one, two and three points received Morris water-maze test to measure searching time on platform (omitting platform-escaping latency). Meanwhile, leaning and memory abilities of animals were reflected through testing times of passing through platform per minute. MAIN OUTCOME MEASURES: Experimental results of omitting platform-escaping latency and spatial probe. RESULTS: Three and two rats in the ischemia/reperfusion group and treatment group respectively were not in accordance with the criteria in the process, and the rest were involved in the final analysis. ① Comparisons of platform-escaping latency during Morris water-maze test in all the three groups: Ten days after modeling, the platform-escaping latency in the ischemia/reperfusion group was obviously longer than that in sham-operation group (P < 0.01), and was significantly shorter than that in the treatment group (P < 0.01). ② Comparisons of times of passing through platform in all the three groups: Times of passing through platform were remarkably less in the ischemia/reperfusion group than those in the sham-operation group [(1.79±0.39), (4.30±0.73) times/minute, P < 0.01], and those were markedly more in the treatment group than the ischemia/reperfusion group [(3.16±1.03), (1.79±0.39) times/minute, P < 0.01]. CONCLUSION: CGRP and NGF are capable of ameliorating the abilities of spatial learning and memory in MCAO rats, which indicates that CGRP and NGF can protect ischemic neurons.展开更多
Objective To investigate the effect and mechanism of adrenomedullin ( AM ) on apoptosis of renal tubular epithelial cell in rats induced by renal ischemia reperfusion injury. Methods Thirty-two Wistar rats were random...Objective To investigate the effect and mechanism of adrenomedullin ( AM ) on apoptosis of renal tubular epithelial cell in rats induced by renal ischemia reperfusion injury. Methods Thirty-two Wistar rats were randomly divided into 4 groups: control group,IRI group, empty plasmid group and AM group. One week after re-展开更多
Epithelial-specific ETS-1(ESE1), a member of the ETS transcription factor family, is widely expressed in multiple tissues and performs various functions in inflammation. During neuroinflammation, ESE1 promotes neurona...Epithelial-specific ETS-1(ESE1), a member of the ETS transcription factor family, is widely expressed in multiple tissues and performs various functions in inflammation. During neuroinflammation, ESE1 promotes neuronal apoptosis; however, the expression and biological functions of ESE1 remain unclear after cerebral ischemia/reperfusion. We performed in vivo and in vitro experiments to explore the role of ESE1 in cerebral ischemic injury. A modified four vessel occlusion method was used in adult Sprague-Dawley rats. At 6, 12, 24, 48, and 72 hours after model induction, the hippocampus was collected for analysis. Western blot assays and immunohistochemistry showed that the expression of ESE1, phosphorylated p65 and active caspase-3 was significantly up-regulated after ischemia. Double immunofluorescence staining indicated that ESE1 and NeuN were mostly co-located in the hippocampus after ischemia. Furthermore, ESE1 was also co-expressed with active caspase-3. PC12 cells were stimulated with cobalt chloride(CoCl_2) to establish a chemical hypoxia model. After ESE1 knockdown by siRNA for 6 hours, cell viability was detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assays. The levels of ESE1, phosphorylated p65 and active caspase-3 were also remarkably increased in PC12 cells after CoCl_2 stimulation. After ESE1 knockdown, PC12 cell viability was increased after hypoxia. siRNA knockdown of ESE1 decreased the level of p-p65 and active caspase-3 after CoCl_2 stimulation. These data reveal that ESE1 levels are elevated in the hippocampus after cerebral ischemia/reperfusion injury. This may play a role in neuronal apoptosis via activation of the nuclear factor-κB pathway.展开更多
Hepatic ischemia-reperfusion injury (IRI) occurs upon restoration of hepatic blood flow after a period of ischemia. Decreased endogenous nitric oxide (NO) production resulting in capillary luminal narrowing is central...Hepatic ischemia-reperfusion injury (IRI) occurs upon restoration of hepatic blood flow after a period of ischemia. Decreased endogenous nitric oxide (NO) production resulting in capillary luminal narrowing is central in the pathogenesis of IRI. Exogenous NO has emerged as a potential therapy for IRI based on its role in decreasing oxidative stress,cytokine release,leukocyte endothelial-adhesion and hepatic apoptosis. This review will highlight the influence of endogenous NO on hepatic IRI,role of inhaled NO in ameliorating IRI,modes of delivery,donor drugs and potential side effects of exogenous NO.展开更多
INTRODUCTIONFrom the technical aspect of liver surgery ,control of bleeding during hepatic parenchymal resection is one of the most important procedures in hepatectomy .Pringle,s maneuver ,a temporary cross-clamping ...INTRODUCTIONFrom the technical aspect of liver surgery ,control of bleeding during hepatic parenchymal resection is one of the most important procedures in hepatectomy .Pringle,s maneuver ,a temporary cross-clamping of the hepatoduodnal ligament ,has often been used for this purpose[1],This is the simplest and userul technique to reduce intraoperative blood loss .展开更多
Myocardial ischemia and reperfusion(I/R) is a common problem in clinic and there is no satisfactory method for prevention or treatment of I/R injury so far.Chronic intermittent hypobaric hypoxia(CIHH),similar to the c...Myocardial ischemia and reperfusion(I/R) is a common problem in clinic and there is no satisfactory method for prevention or treatment of I/R injury so far.Chronic intermittent hypobaric hypoxia(CIHH),similar to the concept of ischemia preconditioning(IPC)or altitude hypoxia adaptation(AHA),has been recognized to confer a protective effect on heart against I/R injury with a longer protective effect than IPC and a less adverse effect than AHA.It has been proved that CIHH increases myocardial tolerance to ischemia or hypoxia,reserving cardiac function and preventing arrhythmia during I/R.Multiple mechanisms or pathway underlying the cardiac protection of CIHH have been proposed,such as induction of heatshock protein,enhancement of myocardial antioxidation capacity,increase of coronary flow and myocardial capillary angiogenesis,activation of adenosine triphosphate(ATP)-sensitive potassium channels,inhibition of mitochondrial permeability transition pores,and activation of protein kinase C(PKC) and induced nitric oxide synthase(iNOS).In addition,CIHH has been found having many beneficial effects on the body,such as promotion of health,increase of oxygen utilization,and prevention or treatment for some diseases.The beneficial effects of CIHH and potential mechanisms are reviewed mainly based on the researches performed by our group.展开更多
Betulin is main component of triterpenoids in bark extract of Betula platyphylla,and has antibacterial,antiviral,liver protecting,cholagogic,antitumorus and other functions.This paper reviews the pharmacological effec...Betulin is main component of triterpenoids in bark extract of Betula platyphylla,and has antibacterial,antiviral,liver protecting,cholagogic,antitumorus and other functions.This paper reviews the pharmacological effects and mechanisms of betulin.展开更多
基金supported by the Natural Science Foundation of Shandong Province,No.ZR2023MC168the National Natural Science Foundation of China,No.31670989the Key R&D Program of Shandong Province,No.2019GSF107037(all to CS).
文摘Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases.However,conventional topical drug delivery often results in a burst release of the drug,leading to transient retention(inefficacy)and undesirable diffusion(toxicity)in vivo.Therefore,a drug delivery system that responds to changes in the microenvironment of tissue regeneration and controls vascular endothelial growth factor release is crucial to improve the treatment of ischemic stroke.Matrix metalloproteinase-2(MMP-2)is gradually upregulated after cerebral ischemia.Herein,vascular endothelial growth factor mimic peptide QK was self-assembled with MMP-2-cleaved peptide PLGLAG(TIMP)and customizable peptide amphiphilic(PA)molecules to construct nanofiber hydrogel PA-TIMP-QK.PA-TIMP-QK was found to control the delivery of QK by MMP-2 upregulation after cerebral ischemia/reperfusion and had a similar biological activity with vascular endothelial growth factor in vitro.The results indicated that PA-TIMP-QK promoted neuronal survival,restored local blood circulation,reduced blood-brain barrier permeability,and restored motor function.These findings suggest that the self-assembling nanofiber hydrogel PA-TIMP-QK may provide an intelligent drug delivery system that responds to the microenvironment and promotes regeneration and repair after cerebral ischemia/reperfusion injury.
文摘BACKGROUND： The majority of studies addressing spinal cord ischemia/reperfusion injury （SCIRI） have focused on drugs, proteins, cytokines, and various surgical techniques. A recent study reports that human umbilical cord mesenchymal stem cell （hUCMSC） transplantation achieves good therapeutic effects, but the mechanisms underlying nerve protection remain poorly understood. OBJECTIVE： To observe survival of transplanted hUCMSCs in SCIRI rat models and the influence on motor function in the hind limbs, to determine interleukin-8 expression and cellular apoptosis in spinal cord tissues, and to verify the hypothesis that hUCMSC transplantation exhibits protective effects on SCIRI. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Laboratory of the Department of Orthopedics in the First Affiliated Hospital of Soochow University, China between January 2007 and December 2008. MATERIALS： hUCMSCs were harvested from umbilical cord blood of healthy pregnant women after parturition in the Obstetrical Department of the First Affiliated Hospital of Soochow University, China. Rabbit anti-human BrdU monoclonal antibody was provided by DAKO, USA. Terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） Kit and enzyme-linked immunosorbent assay （ELISA） Kit were purchased by Wuhan Boster, China. METHODS： A total of 72 healthy, Wistar, adult rats were randomly assigned to three groups： sham-surgery, model, and transplantation, with 24 rats in each group. SCIRI was induced in the model and transplantation groups via the abdominal aorta block method. The infrarenal abdominal aorta was not blocked in the sham-surgery group. Prior to abdominal aorta occlusion, 0.2 03 mL bromodeoxyuridine （BrdU）-Iabeled hUCMSCs suspension （cell concentration 5 × 10 3/uL） was injected through the great saphenous vein of the hind limb, and an equal volume of physiological saline was administered to the model and sham-surgery groups. MAIN OUTCOME MEASURES： Pathological observation of rat spinal cord tissues was performed by hematoxylin-eosin staining at 6, 24, and 48 hours post-surgery. Immunohistochemistry was applied to determine hUCMSCs survival in the spinal cord. The amount of cellular apoptosis and interleukin-8 expression in spinal cord tissues was assayed utilizing the TUNEL and ELISA methods, respectively. Motor function in the hind limbs was evaluated according to Jacob＇s score. RESULTS： Numerous BrdU-positive cells were observed in spinal cord tissues from the transplantation group. The number of apoptotic cells and interleukin-8 levels significantly decreased in the transplantation group （P 〈 0.05）, pathological injury was significantly ameliorated, and motor function scores significantly increased （P 〈 0.05） compared with the model group. CONCLUSION： Via vein transplantation, hUCMSCs were shown to reach and survive in the injury area. Results suggested that the transplanted hUCMSCs contributed to significantly improved pathological changes in the injured spinal cord, as well as motor function, following SCIRI. The protective mechanism correlated with inhibition of cellular apoptosis and reduced production of inflammatory mediators.
文摘BACKGROUND: The fluidity of cell membrane can be affected by various factors. Many experiments have confirmed that the ischemia/reperfusion of organic tissue can increase the contents of free radicals, which lead to high rigidity and low fluidity of cell membrane, and the conditions can be changed by Chuanxiongqin. OBJECTIVE: To observe the effect and mechanism of Chuanxiongqin hydrochloride on the fluidity of brain cell membrane in rat models of ischemia/reperfusion. DESIGN: A completely randomized controlled animal trial. SETTINGS: Institute of Brain Sciences; Department of Physiology, Medical College, Datong University. MATERIALS: Twenty male grade Ⅰ Wistar rats of 170-220 g were randomly divided into model group (n =10) and control group (n =10). Chuanxiongqin hydrochloride (molecular mass was 172.2) was purchased from the National Institute for the Control of Pharmaceutical and Biological Products (batch number: 0817-9803); Spin labelers: 5-doxyl-stearlic acid methylester (5DS), 16-doxyl-stearlic acid methylester (16DS), xanthine, xanthine oxidase (XOD) and 5,5-dimeth-1-pyrroline- N-oxide (DMPO) from Sigma Company; Bruker ESP 300 electron paramagnetic resonance (EPR) spectrometer by Bruker Company (Germany). METHODS: The experiments were carried out in the State Key Laboratory of Natural and Biomimetic Drugs, Peking University from June 2001 to July 2002. In the model group, rats were made into models of cerebral ischemia by 30-minute ligation and 2-hour reperfusion of common carotid arteries; The rats in the control group were not made into models. The order parameter (S) and rotational correlation time (τc) were detected with the ESR spectrometer by means of spin labeling. The greater the S and τc, the smaller the fluidity. Meanwhile, the clearance rate of free radicals was detected with ESR spin trapping. The measurement data were compared using the t test. MAIN OUTCOME MEASURES: The S, τc and clearance rates of O2 · and OH· free radicals were compared between the model group and control group. RESULTS: The S and τc in the model group [0.738 4±0.003 5; (8.472±0.027)×10-10 s/circle] were obviously different from those in the control group [0.683 9±0.008 3; (7.945±0.082)×10-10 s/circle, t =5.731, 5.918, P < 0.05], which suggested that ischemia/reperfusion injury decreased the fluidity of brain cell membrane. After adding Chuanxiongqin hydrochloride, there were no obvious differences between the model group [0.688 5±0.030 5; (7.886±0.341)×10-10 s/circle] and control group (P > 0.05), indicating that Chuanxiongqin hydrochloride could recover the fluidity of brain cell membrane after ischemia/reperfusion injury close to the level in the normal control group. Chuanxiongqin hydrochloride could directly scavenge the O2 · and OH· free radicals, and the maximal clearance rates were 83.92% and 44.99% respectively. CONCLUSION: Chuanxiongqin hydrochloride increases the fluidity of membrane of ischemia-injured brain cell by scavenging both O2 ·and OH· free radicals.
文摘Current antiplatelet drugs mainly focus on prevention rather than the more clinically relevant issue of clearance of an existing thrombus. We recently described a novel and effective therapeutic strategy for dissolution of preexisting platelet thrombus in a murine ischemic stroke model with a bifunctional platelet GPIIIa49-66 ligand (Single-chain antibody Linked first Kringle 1 of plasminogen, named SLK), which homes to newly deposited fibrin strands tangled of platelet thrombus and induces aggregated platelet fragmentation. In this study, we perform in-depth analysis of the effect of SLK on myocardial ischemia-reperfusion (IR) injury in rats. We show that SLK dose-dependently reduces lactate dehydrogenase (LDH) release as well as mean infarction size of left ventricle. Histological observation demonstrates that the arterial thrombi in coronary arteries of rat almost disappear after SLK injection. Optimal dose of SLK (37.5 μg/ individual) provides the myocardial protection at 2 hours post-infusion. However, there are no significant protective effects if SLK was given at 4 or 8 hours post-infusion. The combined application of SLK and urokinase (UK) demonstrates greater myocardial protection than UK alone at 2 hours post-infusion. Thus, SLK could be used as a thrombolytic alternative in other arterial vascular beds associated with thrombosis to enhance fibrinolysis.
文摘Aim Salvia miltiorrhiza Bunge （SM） and lignum dalbergiae odoriferae （DO） are both traditional Chi- nese medicine that have cardioprotective effects. Here, we further examined the combined effects of SM and DO on rat myocardial ischemia/reperfusion injury. The possible mechanism of SM and DO also were elucidated. Methods DO was divided into aqueous extract of lignum dalbergiae odoriferae （DOW） and lignum dalbergiae odoriferae oil （DOO）. Sprague-Dawley rats were randomized to seven groups： sham group, model group, treatment groups inclu- ding SM （10 g · kg^-1）, DOW （5 g · kg^-1）, DOO （0.5 ml · kg^-1）, SM ＋ DOW （10 g · kg^-1 ＋ 5 g · kg^-1）, SM ＋ DOO （ 10 g · kg^-1 ＋ 0. 5 ml · kg^-1）. Rats were pretreated with homologous drug for 7 days and then subjec- ted to 30 rain of ischemia followed by 180 rain of reperfusion. Electrocardiogram （ECG） and heart rate were moni- tored and recorded continuously. At the end of reperfusion, blood samples were collected to determine the serum levels of creatine kinase-MB （CK-MB） and lactate dehydrogenase （LDH）. Hearts were harvested to assess heart- body rate, infarct size and histopathological changes as well. Maximum and minimum effective points were deter- mined by measuring indicators associate with myocardial injury at different time-points of reperfusion （Smin, 15min, 30min, 45rain, 60min, 120min, 180min）. The potential therapeutic mechanism of SM and SM ＋ DOO were carried out by detecting superoxide dismutase （SOD）, malondialdehyde （MDA）, tumor necrosis factor-alpha （TNF-alpha） and interleukin 6 （IL-6）. Results The results showed SM and DO can ameliorate cardiac function respectively, and this cardioprotective effect was further strengthened by their combinations. Among all the combi- nations, SM ＋ DOO showed predominant potential to improve ECG and heart rate, reduce heart-body rate （28.5% ＋ 1.4% , P 〈 0.01 vs model） and myocardial infarct size （ 20.96% ＋ 1.61% , P 〈 0.01 vs model, P 〈 0.05 vs SM） , attenuate histopathological damage, decrease the levels of CK-MB and LDH （P 〈 0.01 vs model, P 〈 0.05 vs SM）. The maximum effective points of SM and SM ＋ DOO were 15min and 30rain respectively, and the minimum effective points of them were 180rain. In reducing serum level of MDA, TNF-alpha, IL-6 and increasing SOD activ- ity, SM ＋ DOO was similar to SM. Conclusion The results of this study indicated that SM ＋ DOO have combined effects that are highly effective than single pretreatment against myocardial ischemie reperfusion injury in rats. The possible mechanism of SM and DO were likely through its anti-oxidant and anti-inflammatory properties, and thus may be an effective and promising medicine for both prophylaxis and treatment of ischemic heart disease.
文摘Objective To study the protecting effects and mechanism of betaine hydrochloride on hepatic ischemia-reperfusion injury in rats.Methods Fourty SD rats were randomly divided into 5 groups(8 animals in each group):sham-operated control group(A),hepatic ischemia-reperfusion group(B),200 mg·kg-1 400 mg·kg-1 800 mg·kg-1 betaine hydrochloride+hepatic ischemia-reperfusion group(C、D、E).betaine hydrochloride was administered to animals byoral route in group C、D、E for 7 days before ischemia.A、B group was administered with NS.Made the animal model of part hepatic ischemia-reperfusion.Serum alanine aminotransferase(ALT),aspartate aminotransferase(AST)levels in the blood and themalondialdehyde(MDA),superoxide dismutase(SOD),protein content in hepatic tissue were determined after the liver had been reperfused for 24 hours;the hepatic tissue was examined under lightmicroscope and the cell apoptosis was demonstrated with flow cytometry.Results ALT,AST,MDA increased and SOD decreased significantly in B group when compared those in the A group(P<0.05),Hepatic apoptosis was significantly increased;ALT,AST,MDA decreased and SOD increased significantly in betaine hydrochloride 200 mg·kg-1(C)group when compared those in the B group(P<0.05).Hepatic apoptosis was significantly lower,The histologic changes of the liver tissue under lightmicroscope in the C group was more easer than in the I/R group(B).Conclusions Betaine hydrochloride has the ability to scavenge oxygen free radical(OFR),reduce lipid peroxidation and inhibition of apoptosis.So it can protect the rats liver damaged by ischemia-reperfusion.
基金the Natural Science Foundation of Shandong Province, No. Y2004C04
文摘BACKGROUND ： The application of exogenous antioxidant is always the focus in the prevention and treatment of cerebral ischemia. Phycocyanin has the effects against oxidation and inflammation, but its role in the pathophysiological process of cerebral ischemia reperfusion injury still needs further investigation. OBJECTIVE： To observe the effects of phycocyanin on the expression of superoxide dismutase （SOD） apoptosis and form of the nerve cells in rats after cerebral ischemia reperfusion injury. DESIGN： A randomized control animal experiment SETTING ： Institute of Cerebrovascular Disease, Medical School Hospital of Qingdao University MATERIALS： Fifty-two healthy adult male Wistar rats of clean degree, weighing 220-260 g, were used. Phycocyanin was provided by the Institute of Oceanology, Chinese Academy of Sciences. METHODS： The experiments were carried out in Shangdong Key Laboratory for Prevention and Treatment of Brain Diseases from May to December 2005. ① All the rats were divided into three groups according to the method of random number table： sham-operated group （n=4）, control group （n=24） and treatment group （n=24）. Models of middle cerebral artery occlusion/reperfusion （MCAO/R） were established by the introduction of thread through external and internal carotid arteries in the control group and treatment group. After 1-hour ischemia and 2-hour reperfusion, rats in the treatment group were administrated with gastric perfusion of phy- cocyanin suspension （0.1 mg/g）, and those in the control group were given saline of the same volume, and no treatment was given to the rats in the sham-operated group. ②The samples were removed and observed at ischemia for 1 hour and reperfusion for 6 and 12 hours and 1, 3, 7 and 14 days respectively in the control group and treatment group, 4 rats for each time point, and those were removed at 1 day postoperatively in the sham-operated group. Forms of the nerve cells were observed with toluidine blue staining. Apoptosis after cerebral ischemia reperfusion was detected with TUNEL technique. SOD expression was detected with immunohistochemical technique.③ The intergroup difference was compared with the ttest. MAIN OUTCOME MEASURES： The apoptosis of the nerve cells and SOD expression were mainly observed in each group. RESULTS： Finally, 52 rats were involved in the analysis of results. ① Number of apoptotic cells： In the sham-operated group, a few apoptotic cells could be observed in brain tissue. The apoptotic cells at each time point in the control group and treatment group were obviously more than those in the sham-operated group （P 〈 0.05）. In the treatment group, the numbers of apoptotic cells at 12 hours, 1 and 3 days after reperfusion were significantly fewer than those in the control group, and those at 6 hours, 7 and 14 days were similar to those in the control group. ② Number of SOD positive cells： In the sham-operated group, there was weak expression of SOD in brain tissue, and the positive cells were extremely few, the positive cells at each time point were significantly more in the control group and treatment group than in the sham-operated group （P 〈 0.05）. In the treatment group, the numbers of positive cells at 6 and 12 hours, 1 and 3 days after reperfusion were significantly fewer than those in the control group, and those at 7-14 days were similar to those in the control group. ③ Cellular forms： In the control group, the karyopyknosis occurred in the nerve cells, which were irregularly distributed, nucleolus disappeared, and some scattered cell fragments were observed. The forms of the nerve cells in the treatment group were generally normal. CONCLUSION ： Phycocyanin plays a neuroprotective role in cerebral ischemia reperfusion injury by activating the SOD expression and inhibiting apoptosis.
文摘Oxidative stress occurs in the organism with ischemia due to tourniquet use and subsequent reperfusion. Oxidative stress increases postoperative morbidity. Some Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) perform their anti-inflammatory effects in part by binding or inhibiting their formation of active oxygen radicals at the site of inflammation. In this study, we aimed to evaluate the effect of IV ibuprofen on ischemia-reperfusion injury (IRI) in patients undergoing total knee arthroplasty over oxidative stress parameters.<span> </span><span>The patients were randomly divided into two groups. Each patient</span><span>’</span><span>s protocol number, age, sex, body mass index (BMI), additional disease, drug use, tourniquet time, hemoglobin value, additional analgesic requirement and application, adverse reaction development on the first postoperative day were recorded in the research follow-up form. Both groups of patients;before anesthesia, 45 minutes after tourniquet application, 5 minutes after tourniquet lowering, 20 minutes after tourniquet lowering and at 24th-hour post-op;TOS, TAS, paraoxonase, arylesterase, myeloperoxidase, catalase, ceruloplasmin, albumin, IMA, thiol-disulfide balance tests were studied. Statistical analysis of test results was performed.</span><span> </span><span>We observed that antioxidants decreased and oxidants increased on the first postoperative day in both groups in patients who underwent total knee arthroplasty. The decrease in antioxidant parameters was higher in IV ibuprofen doses compared to the control group in the case group;these doses indicate that the drug adversely affects the organism in the fight against oxidative stress, which is an undesirable effect. To evaluate this negative effect of IV ibuprofen which is increasingly used in postoperative analgesia, studies with different doses of drugs and different surgeries may be needed.</span>
基金This study is supported by the National Natural Science Foundation of China(No.81303243)Innovation Team of Shaanxi University of Traditional Chinese Medicine(No.2019-QN02)。
文摘Transient receptor potential(TRP)channels are a type of cation channel located on the cell membrane.TRP channels are divided into 7 subfamilies(TRPC,TRPA,TRPM,TRPV,TRPN,TRPP and TRPML)and widely expressed in myocardial tissue.In recent years,with the application of gene knockout and transgenic model animals,it has been found that members of the TRP channel subfamilies TRPM,TRPC and TRPV are closely related to myocardial ischemia-reperfusion injury.The activation or inhibition of TRP channels participates in the regulation of myocardial ischemia-reperfusion injury,reduces the infarct area of the myocardium,and exerts a protective effect.Therefore,this paper first summarizes the structural characteristics of TRPM,TRPC,and TRPV and their distribution in the cardiovascular system,and then summarizes the mechanisms of TRPM,TRPC,and TRPV that regulate myocardial ischemia and reperfusion,which will provide a certain theoretical basis for treatment of myocardial ischemia-reperfusion injury.
文摘BACKGROUND: Calcitonin gene-related peptide (CGRP) and nerve growth actor (NGF) cam improve spatial learning and memory abilities of rats with cerebral ischemia/reperfusion; however, the effect of combination of them on relieving learning and memory injury following cerebral ischemia/reperfusion should be further studied. OBJECTIVE: To study the effects of exogenous CGRP and NGF on learning and memory abilities of rats with focal cerebral ischemia/reperfusion. DESIGN: Randomized controlled animal study. SETTING: Department of Neurosurgery, the Second Hospital of Xiamen; Department of Neurosurgery, the Second Affiliated Hospital of China Medical University; Department of Neurobiology, Basic Medical College of China Medical University. MATERIALS: A total of 30 healthy male SD rats, aged 8 weeks, of clean grade, weighing 250-300 g, were provided by Experimental Animal Department of China Medical University. All rats were randomly divided into sham-operation group, ischemia/reperfusion group and treatment group with 10 in each group. The main reagents were detailed as the follows: 100 g/L chloral hydrate, 0.5 mL CGRP (2 mg/L, Sigma Company, USA), and NGF (1× 106 U/L, 0.5 mL, Siweite Company, Dalian). METHODS: The experiment was carried out in the Department of Neurobiology, Basic Medical College of China Medical University from February to July 2005. Rat models of middle cerebral artery occlusion were established by method of occlusion, 2 hours after that rats were anesthetized and the thread was slightly drawn out for 10 mm under direct staring to perform reperfusion. Rats in the ischemia/reperfusion group received intraperitoneal injection of 1 mL saline via the abdomen at two hours later, while rats in the treatment group at 2 hours later received intraperitoneal injection of 2 mg/L CGRP (0.5 mL) and 1×106 U/L NGF (0.5 mL) once a day for 10 successive days. First administration was accomplished within 15 minutes after ischemia/reperfusion. Rats in the sham-operation group were separated of the vessels without occlusion or administration. The neural function was evaluated with Zea Longa 5-grade scale. Animals with the score of one, two and three points received Morris water-maze test to measure searching time on platform (omitting platform-escaping latency). Meanwhile, leaning and memory abilities of animals were reflected through testing times of passing through platform per minute. MAIN OUTCOME MEASURES: Experimental results of omitting platform-escaping latency and spatial probe. RESULTS: Three and two rats in the ischemia/reperfusion group and treatment group respectively were not in accordance with the criteria in the process, and the rest were involved in the final analysis. ① Comparisons of platform-escaping latency during Morris water-maze test in all the three groups: Ten days after modeling, the platform-escaping latency in the ischemia/reperfusion group was obviously longer than that in sham-operation group (P < 0.01), and was significantly shorter than that in the treatment group (P < 0.01). ② Comparisons of times of passing through platform in all the three groups: Times of passing through platform were remarkably less in the ischemia/reperfusion group than those in the sham-operation group [(1.79±0.39), (4.30±0.73) times/minute, P < 0.01], and those were markedly more in the treatment group than the ischemia/reperfusion group [(3.16±1.03), (1.79±0.39) times/minute, P < 0.01]. CONCLUSION: CGRP and NGF are capable of ameliorating the abilities of spatial learning and memory in MCAO rats, which indicates that CGRP and NGF can protect ischemic neurons.
文摘Objective To investigate the effect and mechanism of adrenomedullin ( AM ) on apoptosis of renal tubular epithelial cell in rats induced by renal ischemia reperfusion injury. Methods Thirty-two Wistar rats were randomly divided into 4 groups: control group,IRI group, empty plasmid group and AM group. One week after re-
基金supported by the National Natural Science Foundation of China,No.81400963(to HLY)the 333 Project of Jiangsu Province of China,No.BRA2015187(to YZC)the Medical Youth Talent Foundation of Jiangsu Province of China,No.QNRC2016327(to HLY),QNRC2016328(to BLC),and QNRC2016326(to YPL)
文摘Epithelial-specific ETS-1(ESE1), a member of the ETS transcription factor family, is widely expressed in multiple tissues and performs various functions in inflammation. During neuroinflammation, ESE1 promotes neuronal apoptosis; however, the expression and biological functions of ESE1 remain unclear after cerebral ischemia/reperfusion. We performed in vivo and in vitro experiments to explore the role of ESE1 in cerebral ischemic injury. A modified four vessel occlusion method was used in adult Sprague-Dawley rats. At 6, 12, 24, 48, and 72 hours after model induction, the hippocampus was collected for analysis. Western blot assays and immunohistochemistry showed that the expression of ESE1, phosphorylated p65 and active caspase-3 was significantly up-regulated after ischemia. Double immunofluorescence staining indicated that ESE1 and NeuN were mostly co-located in the hippocampus after ischemia. Furthermore, ESE1 was also co-expressed with active caspase-3. PC12 cells were stimulated with cobalt chloride(CoCl_2) to establish a chemical hypoxia model. After ESE1 knockdown by siRNA for 6 hours, cell viability was detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assays. The levels of ESE1, phosphorylated p65 and active caspase-3 were also remarkably increased in PC12 cells after CoCl_2 stimulation. After ESE1 knockdown, PC12 cell viability was increased after hypoxia. siRNA knockdown of ESE1 decreased the level of p-p65 and active caspase-3 after CoCl_2 stimulation. These data reveal that ESE1 levels are elevated in the hippocampus after cerebral ischemia/reperfusion injury. This may play a role in neuronal apoptosis via activation of the nuclear factor-κB pathway.
文摘Hepatic ischemia-reperfusion injury (IRI) occurs upon restoration of hepatic blood flow after a period of ischemia. Decreased endogenous nitric oxide (NO) production resulting in capillary luminal narrowing is central in the pathogenesis of IRI. Exogenous NO has emerged as a potential therapy for IRI based on its role in decreasing oxidative stress,cytokine release,leukocyte endothelial-adhesion and hepatic apoptosis. This review will highlight the influence of endogenous NO on hepatic IRI,role of inhaled NO in ameliorating IRI,modes of delivery,donor drugs and potential side effects of exogenous NO.
基金This work was supported partly by Grant 90089102 from the Scientific Research Fund of the Ministry of Education,Japan
文摘INTRODUCTIONFrom the technical aspect of liver surgery ,control of bleeding during hepatic parenchymal resection is one of the most important procedures in hepatectomy .Pringle,s maneuver ,a temporary cross-clamping of the hepatoduodnal ligament ,has often been used for this purpose[1],This is the simplest and userul technique to reduce intraoperative blood loss .
基金supported by National Basic Research Program of China(2006CB504100,2012CB518200)National Natural Science Foundation(30393130,31071002)+1 种基金Science and Technology committee of Shanghai Municipality(02JC14038)Science and technology program of Hebei province(09276115)
文摘Myocardial ischemia and reperfusion(I/R) is a common problem in clinic and there is no satisfactory method for prevention or treatment of I/R injury so far.Chronic intermittent hypobaric hypoxia(CIHH),similar to the concept of ischemia preconditioning(IPC)or altitude hypoxia adaptation(AHA),has been recognized to confer a protective effect on heart against I/R injury with a longer protective effect than IPC and a less adverse effect than AHA.It has been proved that CIHH increases myocardial tolerance to ischemia or hypoxia,reserving cardiac function and preventing arrhythmia during I/R.Multiple mechanisms or pathway underlying the cardiac protection of CIHH have been proposed,such as induction of heatshock protein,enhancement of myocardial antioxidation capacity,increase of coronary flow and myocardial capillary angiogenesis,activation of adenosine triphosphate(ATP)-sensitive potassium channels,inhibition of mitochondrial permeability transition pores,and activation of protein kinase C(PKC) and induced nitric oxide synthase(iNOS).In addition,CIHH has been found having many beneficial effects on the body,such as promotion of health,increase of oxygen utilization,and prevention or treatment for some diseases.The beneficial effects of CIHH and potential mechanisms are reviewed mainly based on the researches performed by our group.
基金Supported by Talent Training Project of the Central Support Fund for the Reform and Development of Local Colleges and Universities(2020GSP16)。
文摘Betulin is main component of triterpenoids in bark extract of Betula platyphylla,and has antibacterial,antiviral,liver protecting,cholagogic,antitumorus and other functions.This paper reviews the pharmacological effects and mechanisms of betulin.
