Continuous Monitoring of Serum Tumor Necrosis Factor-α for Patients with TEMIS Treated by Nitrates Postconditioning during PCI

Objective: To investigate the protective effect of nitrates postconditioning on myocardial ischemia-reperfusion injury and whether it plays a regulatory role in TNF-α in patients with STEMI during PCI. Methods: Patients with STEMI who underwent PCI were selected, except for obvious anemia, head trauma, cerebral hemorrhage, hypotension (systolic blood pressure less than 90 mmHg), and patients with autoimmune diseases, all kinds of acute and chronic infections and malignant tumors. They were randomly divided into PCI standardized treatment group and isosorbide dinitrate postconditioning during PCI group. The concentrations of cTnI and TNF-α in serum were detected by ELISA method in each group before PCI and after 2 hours, 1 day, 4 days and 7 days of PCI. Results: 1) There were no statistically significant differences in sex, age, smoking history, diabetes, hypertension and blood lipid abnormality in two groups. 2) Before operation, the concentration of cTnI in two groups was not statistically significant. The concentration of cTnI in the experimental group was lower than that of the control group after 4 days and 7 days of PCI, and P α in two groups before operation. The concentration of TNF-α in the experimental group was lower than that in the control group after 1 day, 4 days and 7 days of PCI, and P α in two groups was both in 1 day after operation, and the peak level of the experimental group and the level of each time after the operation were lower than that of the control group. Conclusion: Nitrates postconditioning during PCI in patients with STEMI has a protective effect on myocardial ischemia-reperfusion injury. Nitrates postconditioning has an effect to reduce the level of TNF-α of patients with STEMI after PCI treatment, and may have the mechanism of alleviating the inflammatory response after myocardial ischemia and reperfusion.

Effect of Minocycline Postconditioning and Ischemic Postconditioning on Myocardial Ischemia-reperfusion Injury in Atherosclerosis Rabbits

This study examined the protective effect of ischemic postconditioning(IPoC) and minocycline postconditioning(MT) on myocardial ischemia-reperfusion(I/R) injury in atherosclerosis(AS) animals and the possible mechanism.Forty male healthy rabbits were injected with bovine serum albumin following feeding on a high fat diet for 6 weeks to establish AS model.AS rabbits were randomly divided into 3 groups:(1) I/R group,the rabbits were subjected to myocardial ischemia for 35 min and then reperfusion for 12 h;(2) IPoC group,the myocardial ischemia lasted for 35 min,and then reperfusion for 20 s and ischemia for 20 s [a total of 3 cycles(R20s/I20s×3)],and then reperfusion was sustained for 12 h;(3) MT group,minocycline was intravenously injected 10 min before reperfusion.The blood lipids,malondialdehyde(MDA),superoxide dismutase(SOD),soluble cell adhesion molecule(sICAM),myeloperoxidase(MPO),and cardiac troponin T(cTnT) were biochemically determined.The myocardial infarction size(IS) and apoptosis index(AI) were measured by pathological examination.The expression of bcl-2 and caspase-3 was detected in the myocardial tissue by using reverse transcription-polymerase chain reaction(RT-PCR).The results showed that the AS models were successfully established.The myocardial IS,the plasma levels of MDA,sICAM,MPO and cTnT,and the enzymatic activity of MPO were significantly decreased,and the plasma SOD activity was significantly increased in IPoC group and MT group as compared with I/R group(P<0.05 for all).The myocardial AI and the caspase-3 mRNA expression were lower and the bcl-2 mRNA expression was higher in IPoC and MT groups than those in I/R group(all P<0.05).It is concluded that the IPoC and MT can effectively reduce the I/R injury in the AS rabbits,and the mechanisms involved anti-oxidation,anti-inflammation,up-regulation of bcl-2 expression and down-regulation of caspase-3 expression.Minocycline can be used as an effective pharmacologic postconditioning drug to protect myocardia from I/R injury.

Postconditioning of sevoflurane and propofol is associated with mitochondrial permeability transition pore

Background: Sevoflurane and propofol are effective cardioprotective anaesthetic agents, though the cardioprotection of propofol has not been shown in humans. Their roles and underlying mechanisms in anesthetic postconditioning are unclear. Mitochondrial permeability transition pore (MPTP) opening is a major cause of ischemia-reperfusion injury. Here we investigated sevoflurane- and propofol-induced postconditioning and their relationship with MPTP. Methods: Isolated perfused rat hearts were exposed to 40 min of ischemia followed by 1 h of reperfusion. During the first 15 min of reperfusion, hearts were treated with either control buffer (CTRL group) or buffer containing 20 μmol/L atractyloside (ATR group), 3% (v/v) sevoflurane (SPC group), 50 μmol/L propofol (PPC group), or the combination of atractyloside with respective anesthetics (SPC+ATR and PPC+ATR groups). Infarct size was determined by dividing the total necrotic area of the left ventricle by the total left ventricular slice area (percent necrotic area). Results: Hearts treated with sevoflurane or propofol showed significantly better recovery of coronary flow, end-diastolic pressures, left ventricular developed pressure and derivatives compared with controls. Sevoflurane resulted in more protective alteration of hemodynamics at most time point of reperfusion than propofol. These improvements were paralleled with the reduction of lactate dehydrogenase release and the decrease of infarct size (SPC vs CTRL: (17.48±2.70)% vs (48.47±6.03)%, P<0.05; PPC vs CTRL: (35.60±2.10)% vs (48.47±6.03)%, P<0.05). SPC group had less infarct size than PPC group (SPC vs PPC: (17.48±2.70)% vs (35.60±2.10)%, P<0.05). Atractyloside coadministration attenuated or completely blocked the cardioprotective effect of postconditioning of sevoflurane and propofol. Conclusion: Postconditioning of sevoflurane and propofol has cardio-protective effect against ischemia-reperfusion injury of heart, which is associated with inhibition of MPTP opening. Compared to propofol, sevoflurane provides superior protection of functional recovery and infarct size.

A feasible strategy for focal cerebral ischemiareperfusion injury: remote ischemic postconditioning

It is difficult to control the degree of ischemic postconditioning in the brain and other isch- emia-sensitive organs. Remote ischemic postconditioning could protect some ischemia-sensitive organs through measures on terminal organs. In this study, a focal cerebral ischemia-reperftlsion injury model was established using three cycles of remote ischernic postconditioning, each cycle consisted of 10-minute occlusion of the femoral artery and 10-minute opening. The results showed that, remote ischemic postconditioning significantly decreased the percentage of the in- farct area and attenuated brain edema. In addition, inflammatory nuclear factor-KB expression was significantly lower, while anti-apoptotic Bcl-2 expression was significantly elevated in the ce- rebral cortex on the ischemic side. Our findings indicate that remote ischemic postconditioning attenuates focal cerebral ischemia/reperfusion injury, and that the neuroprotective mechanism is mediated by an anti-apoptotic effect and reduction of the inflammatory response.

Preconditioning and postconditioning reduce hepatic ischemia-reperfusion injury in rats

BACKGROUND: Ischemia-reperfusion injury occurs when ischemic tissues or organs suffer from further functional and structural damage when their blood supply recovers. This study aimed to contrast the protective effects of ischemic preconditioning and ischemic postconditioning in hepatic ischemia-reperfusion injury in rats. METHODS: Thirty-two healthy male Wistar rats were randomly divided into four groups: sham-operated (SO), ischemia-reperfusion (IR), ischemic preconditioning (I-pre), and ischemic postconditioning (I-post). Blood samples and hepatic tissue were taken from all groups after the experiments. RESULTS: There were significant differences between the IR, I-pre and I-post groups in alanine aminotransferase and aspartate aminotransferase levels, NF-kappa B p65 expression, apoptosis index and superoxide dismutase activity in hepatic tissue. There were no significant differences between the I-pre and I-post groups. CONCLUSIONS: Ischemic postconditioning and ischemic preconditioning reduce hepatic ischemia-reperfusion injury, but in clinical practice the former is a more appropriate choice.

Limb remote ischemic postconditioning protects integrity of the blood-brain barrier after stroke

Integrity of the blood-brain barrier structure is essential for maintaining the internal environment of the brain.Development of cerebral infarction and brain edema is strongly associated with blood-brain barrier leakage.Therefore,studies have suggested that protecting the blood-brain barrier may be an effective method for treating acute stroke.To examine this possibility,stroke model rats were established by middle cerebral artery occlusion and reperfusion.Remote ischemic postconditioning was immediately induced by three cycles of 10-minute ischemia/10-minute reperfusion of bilateral hind limbs at the beginning of middle cerebral artery occlusion reperfusion.Neurological function of rat models was evaluated using Zea Longa’s method.Permeability of the blood-brain barrier was assessed by Evans blue leakage.Infarct volume and brain edema were evaluated using 2,3,5-triphenyltetrazolium chloride staining.Expression of matrix metalloproteinase-9 and claudin-5 m RNA was determined by real-time quantitative reverse transcription-polymerase chain reaction.Expression of matrix metalloproteinase-9 and claudin-5 protein was measured by western blot assay.The number of matrix metalloproteinase-9-and claudin-5-positive cells was analyzed using immunohistochemistry.Our results showed that remote ischemic postconditioning alleviated disruption of the blood-brain barrier,reduced infarct volume and edema,decreased expression of matrix metalloproteinase-9 m RNA and protein and the number of positive cells,increased expression of claudin-5 m RNA and protein and the number of positive cells,and remarkably improved neurological function.These findings confirm that by suppressing expression of matrix metalloproteinase-9 and claudin-5 induced by acute ischemia/reperfusion,remote ischemic postconditioning reduces blood-brain barrier injury,mitigates ischemic injury,and exerts protective effects on the brain.

Propofol postconditioning ameliorates hypoxia/reoxygenation induced H9c2 cell apoptosis and autophagy via upregulating forkhead transcription factors under hyperglycemia

Background:Administration of propofol,an intravenous anesthetic with antioxidant property,immediately at the onset of post-ischemic reperfusion(propofol postconditioning,P-PostC) has been shown to confer cardioprotection against ischemia–reperfusion(I/R) injury,while the underlying mechanism remains incompletely understood.The forkhead box O(FoxO) transcription factors are reported to play critical roles in activating cardiomyocyte survival signaling throughout the process of cellular injuries induced by oxidative stress and are also involved in hypoxic postconditioning mediated neuroprotection,however,the role of FoxO in postconditioning mediated protection in the heart and in particular in high glucose condition is unknown.Methods:Rat heart-derived H9c2 cells were exposed to high glucose(HG) for 48 h,then subjected to hypoxia/reoxygenation(H/R,composed of 8 h of hypoxia followed by 12 h of reoxygenation) in the absence or presence of postconditioning with various concentrations of propofol(P-PostC) at the onset of reoxygenation.After having identified the optical concentration of propofol,H9c2 cells were subjected to H/R and P-PostC in the absence or presence of FoxO1 or FoxO3a gene silencing to explore their roles in P-PostC mediated protection against apoptotic and autophagic cell deaths under hyperglycemia.Results:The results showed that HG with or without H/R decreased cell viability,increased lactate dehydrogenase(LDH) leakage and the production of reactive oxygen species(ROS) in H9c2 cells,all of which were significantly reversed by propofol(P-PostC),especially at the concentration of 25 μmol/L(P25)(P<0.05,NC vs.HG;HG vs.HG+HR;HG+HR+P12.5 or HG+HR+P25 or HG+HR+P50 vs.HG+HR).Moreover,we found that propofol(P25) decreased H9c2 cells apoptosis and autophagy that were concomitant with increased FoxO1 and FoxO3a expression(P<0.05,HG+HR+P25 vs.HG+HR).The protective effects of propofol(P25) against H/R injury were reversed by silencing FoxO1 or FoxO3a(P<0.05,HG+HR+P25 vs.HG+HR+P25+siRNA-1 or HG+HR+P25+siRNA-5).Conclusions:It is concluded that propofol postconditioning attenuated H9c2 cardiac cells apoptosis and autophagy induced by H/R injury through upregulating FoxO1 and FoxO3a under hyperglycemia.

Neuroprotective effects of long noncoding RNAs involved in ischemic postconditioning after ischemic stroke

During acute reperfusion,the expression profiles of long noncoding RNAs in adult rats with focal cerebral ischemia undergo broad changes.However,whether long noncoding RNAs are involved in neuroprotective effects following focal ischemic stroke in rats remains unclear.In this study,RNA isolation and library preparation was performed for long noncoding RNA sequencing,followed by determining the coding potential of identified long noncoding RNAs and target gene prediction.Differential expression analysis,long noncoding RNA functional enrichment analysis,and co-expression network analysis were performed comparing ischemic rats with and without ischemic postconditioning rats.Rats were subjected to ischemic postconditioning via the brief and repeated occlusion of the middle cerebral artery or femoral artery.Quantitative real-time reverse transcription-polymerase chain reaction was used to detect the expression levels of differentially expressed long noncoding RNAs after ischemic postconditioning in a rat model of ischemic stroke.The results showed that ischemic postconditioning greatly affected the expression profile of long noncoding RNAs and mRNAs in the brains of rats that underwent ischemic stroke.The predicted target genes of some of the identified long noncoding RNAs(cis targets)were related to the cellular response to ischemia and stress,cytokine signal transduction,inflammation,and apoptosis signal transduction pathways.In addition,15 significantly differentially expressed long noncoding RNAs were identified in the brains of rats subjected to ischemic postconditioning.Nine candidate long noncoding RNAs that may be related to ischemic postconditioning were identified by a long noncoding RNA expression profile and long noncoding RNA-mRNA co-expression network analysis.Expression levels were verified by quantitative real-time reverse transcription-polymerase chain reaction.These results suggested that the identified long noncoding RNAs may be involved in the neuroprotective effects associated with ischemic postconditioning following ischemic stroke.The experimental animal procedures were approved by the Animal Experiment Ethics Committee of Kunming Medical University(approval No.KMMU2018018)in January 2018.

Postconditioning’s Protection of THSG on Cardiac Ischemia-reperfusion Injury and Mechanism

2,3,5,4＇-tetra-hydroxystilbene-2-O-glucoside （THSG）, the water-soluble active components extracted from dried tuber root of Polygonum multiflorurn （Polygonaceae）, can promote the release of nitric oxide （NO） from vascular endothelial cells and has strong antioxidation. The postconditioning＇s protection of THSG on cardiac ischemia-reperfusion injury and the mechanism were investigated. After reperfusion for 3 h following occlusion of rat left anterior descending coronary artery （LAD） for 30 min, SαT recovery speed, arrhythmia and cardiac infarct size were observed. The ischemic size and infarct size was identified by using Evans blue and TTC staining methods respectively. The results showed that the infarct size in THSG 7.5 mg/kg postconditioning group was significantly decreased from 43.6 %± 9.1% in mode group to 16.5% ±6.5% （P〈0.01）. SaT recovery was quicker and the incidence of arrhythmia （55.6 % vs 100 %, P〈0.05） was significantly lower than in control group. The infarct size in THSG＋glybenclamide group was greater than in THSG group, but equivalent to that in control group （46.8 %±9.8 % vs 43. 6 %±9.1%, P〉0. 05）, SaT recovery speed slower and the incidence of arrhythmia also lower （33.3% vs 100%, P〈0.01）, suggesting that glybenclamide could abolish the effects of THSG postconditioning reducing the cardiac infart size. It was concluded that THSG administration before reperfusion could effectively alleviate the cardiac reperfusion injury and possessed the postconditioning effects of reducing cardiac infarct size, which might be related with the KATe channel opening.

Ischemic postconditioning enhances glycogen synthase kinase-3β expression and alleviates cerebral ischemia/reperfusion injury

The present study established global brain ischemia using the four-vessel occlusion method. Following three rounds of reperfusion for 30 seconds, and occlusion for 10 seconds, followed by reperfusion for 48 hours, infarct area, the number of TUNEL-positive cells and Bcl-2 expression were significantly reduced. However, glycogen synthase kinase-3β activity, cortical Bax and caspase-3 expression significantly increased, similar to results following ischemic postconditioning. Our results indicated that ischemic postconditioning may enhance glycogen synthase kinase-3β activity, a downstream molecule of the phosphatase and tensin homolog deleted on chromosome 10/phosphatidylinositol 3-kinase/protein kinase B signaling pathway, which reduces caspase-3 expression to protect the brain against ischemic injury.

Remote ischemic postconditioning protects against gastric mucosal lesions in rats

AIM: To investigate the protective effects of remote ischemic postconditioning (RIP) against limb ischemia-reperfusion (IR)-induced gastric mucosal injury.

Neuroprotective effect of ischemic postconditioning on sciatic nerve transection

Ischemic preconditioning or postconditioning has been shown to have neuroprotective effect on cerebral ischemia, but it has not been studied in peripheral nerve injury. In this study, a rat model of sciatic nerve transection was established, and subjected to three cycles of ischemia for 10 minutes ＋ reperfusion for 10 minutes, once a day. After ischemic postconditioning, serum insulin-like growth factor 1 expression increased; sciatic nerve Schwann cell myelination increased; sensory function and motor function were restored. These findings indicate that ischemic postconditioning can effectively protect injured sciatic nerve. The protective effect is possibly associated with upregulation of insulin-like growth factor 1.

Ischemic postconditioning protects against ischemic brain injury by up-regulation of acid-sensing ion channel 2a

Ischemic postconditioning renders brain tissue tolerant to brain ischemia,thereby alleviating ischemic brain injury.However,the exact mechanism of action is still unclear.In this study,a rat model of global brain ischemia was subjected to ischemic postconditioning treatment using the vessel occlusion method.After 2 hours of ischemia,the bilateral common carotid arteries were blocked immediately for 10 seconds and then perfused for 10 seconds.This procedure was repeated six times.Ischemic postconditioning was found to mitigate hippocampal CA1 neuronal damage in rats with brain ischemia,and up-regulate acid-sensing ion channel 2a expression at the m RNA and protein level.These findings suggest that ischemic postconditioning up-regulates acid-sensing ion channel 2a expression in the rat hippocampus after global brain ischemia,which promotes neuronal tolerance to ischemic brain injury.

Optimized postconditioning algorithm protects liver graft after liver transplantation in rats

Background: Ischemia reperfusion injury(IRI) causes postoperative complications and influences the outcome of the patients undergoing liver surgery and transplantation. Postconditioning(Post C) is a known manual conditioning to decrease the hepatic IRI. Here we aimed to optimize the applicable Post C protocols and investigate the potential protective mechanism.Methods: Thirty Sprague–Dawley rats were randomly divided into 3 groups: the sham group(n = 5),standard orthotopic liver transplantation group(OLT, n = 5), Post C group(OLT followed by clamping and re-opening the portal vein for different time intervals, n = 20). Post C group was then subdivided into 4 groups according to the different time intervals:(10 s × 3, 10 s × 6, 30 s × 3, 60 s × 3, n = 5 in each subgroup). Liver function, histopathology, malondialdehyde(MDA), myeloperoxidase(MPO), expressions of p-Akt and endoplasmic reticulum stress(ERS) related genes were evaluated.Results: Compared to the OLT group, the grafts subjected to Post C algorithm(without significant prolonging the total ischemic time) especially with short stimulus and more cycles(10 s × 6) showed significant alleviation of morphological damage and graft function. Besides, the production of reactive oxidative agents(MDA) and neutrophil infiltration(MPO) were significantly depressed by Post C algorithm. Most of ERS related genes were down-regulated by Post C(10 s × 6), especially ATF4, Casp12, hspa4, ATF6 and ELF2, while p-Akt was up-regulated.Conclusions: Post C algorithm, especially 10 s × 6 algorithm, showed to be effective against rat liver graft IRI. These protective effects may be associated with its antioxidant, inhibition of ERS and activation of p-Akt expression of reperfusion injury salvage kinase pathway.

Protection of ghrelin postconditioning on hypoxia/ reoxygenation in gastric epithelial cells

AIM: To investigate the protective effect and mechanisms of ghrelin postconditioning against hypoxia/reoxygenation (H/R)-induced injury in human gastric epithelial cells. METHODS: The model of H/R injury was established in gastric epithelial cell line (GES-1) human gastric epithelial cells. Cells were divided into seven groups: normal control group (N); H/R postconditioning group; DMSO postconditioning group (DM); ghrelin postconditioning group (GH); D-Lys3-GHRP-6 + ghrelin postconditioning group (D + GH); capsazepine + ghrelin postconditioning group (C + GH); and LY294002 + ghrelin postconditioning group (L + GH). 3-(4,5-dimethylthazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was used to detect GES-1 cell viability. Hoechst 33258 fluorochrome staining and flow cytometry were conducted to determine apoptosis of GES-1cells. Spectrophotometry was performed to determine release of lactate dehydrogenate (LDH). Protein expression of Bcl-2, Bax, Akt, and glycogen synthase kinase (GSK)-3β was determined by western blotting. Expression of vanilloid receptor subtype 1 (VR1), Akt and GSK-3β was observed by immunocytochemistry. RESULTS: Compared with the H/R group, cell viability of the GH group was significantly increased in a dosedependent manner (55.9% ± 10.0% vs 69.6% ± 9.6%, 71.9% ± 17.4%, and 76.3% ± 13.3%). Compared with the H/R group, the percentage of apoptotic cells in the GH group significantly decreased (12.38% ± 1.51% vs 6.88% ± 0.87%). Compared with the GH group, the percentage of apoptotic cells in the D + GH group, C + GH group and L + GH groups significantly increased (11.70% ± 0.88%, 11.93% ± 0.96%, 10.20% ± 1.05% vs 6.88% ± 0.87%). There were no significant differences in the percentage of apoptotic cells between the H/R and DM groups (12.38% ± 1.51% vs 13.00% ± 1.13%). There was a significant decrease in LDH release following ghrelin postconditioning compared with the H/R group (561.58 ± 64.01 U/L vs 1062.45 ± 105.29 U/L). There was a significant increase in LDH release in the D + GH, C + GH and L + GH groups compared with the GH group (816.89 ± 94.87 U/L, 870.95 ± 64.06 U/L, 838.62 ± 118.45 U/L vs 561.58 ± 64.01 U/L). There were no significant differences in LDH release between the H/R and DM groups (1062.45 ± 105.29 U/L vs 1017.65 ± 68.90 U/L). Compared with the H/R group, expression of Bcl-2 and Akt increased in the GH group, whereas expression of Bax and GSK3β decreased. Compared with the GH group, expression of Bcl-2 decreased and Bax increased in the D + GH, C + GH and L + GH groups, and Akt decreased and GSK-3β increased in the L + GH group. The H/R group also upregulated expression of VR1 and GSK-3β and downregulated Akt. The number of VR1-positive and Akt-positive cells in the GH group significantly increased, whereas the number of GSK-3β-positive cells significantly decreased. These effects of ghrelin were reversed by capsazepine and LY294002.CONCLUSION: Ghrelin postconditioning protected against H/R-induced injury in human gastric epithelial cells, which indicated that this protection might be associated with GHS-R, VR1 and the PI3K/Akt signaling pathway.

Effects of isoflurane and sevoflurane postconditioning and changes in JNK1/2 pathway activity on rat brain slices subjected to oxygen and glucose deprivation in vitro

Recent research shows that the JNK1/2 signaling pathway plays a neuroprotective role against ischemia-reperfusion injury by cross-talk with other pathways.The present study investigated the effects of isoflurane and sevoflurane postconditioning on JNK1/2 pathway activity and neuronal cell viability after oxygen and glucose deprivation injury in hippocampal slices in vitro.Techniques used included population spike analysis,propidium iodide fluorescent staining,western blot assay,and the use of JNK1/2-specific pharmacological tools such as anisomycin （agonist） and SP600125 （inhibitor）.We found that both isoflurane and sevoflurane inhibited JNK pathway activity and had neuroprotective effects against oxygen and glucose deprivation injury in slices of rat hippocampus in vitro.Postconditioning with volatile anesthetics exerted neuroprotective effects on nerve cells and preserved the function of the CA1 region by inhibiting JNK1/2 phosphorylation.This suppression of JNK1/2 activity could underlie the observed synergistic neuroprotective effect produced by volatile anesthetic postconditioning.

Sevoflurane preconditioning and postconditioning attenuate apoptosis induced by ischemia-reperfusion in rat lung

Objective To investigate the effect of sevoflurane preconditioning and postconditioning on lung ischemia-reperfusion(IR) injury and apoptosis in rat.Methods Wistar rats were randomly assigned to four groups:sham group(n =6):no ischaemia-reperfusion;IR group(n =6):left lung ischemia was achieved by clamping the hilum for 90 min,followed by 120 min reperfusion;sev+pre group(n =6):1 minimum alveolar concentration(MAC) sevoflurane was admi-nistered for 30 min prior to ischemia;sev+post group(n =6):ischemia was followed by 1 MAC sevoflurane postconditioning at the first 30 min reperfusion.PaO2 was measured after reperfusion.The number of apoptotic cells was estimated using the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling(TUNEL) technique.Results After ischemia-reperfusion,a significant deterioration of PaO2 was noticed and the number of apoptotic cells remarkably increased compared with that of sham group.In sev+pre group and sev+post group,PaO2 was(85.7±14.4) mmHg and(88.6±12.5) mmHg respectively,which was apparently increased compared with that in IR group [(63.9±11.3) mmHg,P <0.05].The number of apoptotic cells in sev+pre group [(6.94 ± 1.49)%] and sev+post group [(7.69 ± 1.61)%] was significantly lower than that in IR group [(12.12 ± 2.77)%,P <0.05].But all parameters showed no significant difference between sev+pre group and sev+post group.Conclusions Both sevoflurane preconditioning and postconditioning could prevent lung ischemia-reperfusion injury and attenuate apoptosis in rat.

Spontaneous running wheel improves neuroprotection efficacy of ischemic postconditioning in mice following ischemia/reperfusion injury

Ischemic postconditioning(IP)has been shown to provide protection for ischemia/reperfusion(IR)injury,but its efficacy is limited.In this study we hypothesized that spontaneous running wheel(RW)could improve neuroprotection efficacy of IP for IR.We established mouse models of IR and showed that compared to Sham group,IR group had obvious brain infract and neurological dysfunction.In IR+IP group,brain infract and neurological dysfunction improved compared to IR group.However,in IR+IP+RW group brain infract and neurological dysfunction improved much better.TUNEL assay showed that IP but not RW significantly reduced the number of apoptotic cells after IR.However,the number of apoptotic cells was significantly reduced in RW+IP group.In addition,the levels of pro-apoptotic factors increased in IR group but significantly reduced in IR+IP+RW group,while the levels of antiapoptotic factors decreased in IR group but significantly increased in IR+IP+RW group.Moreover,in IR+IP+RW group,MDA level was further decreased and SOD level was further increased compared to IR+IP group.Finally,both PI3K inhibitor and STAT3 inhibitor significantly worsened brain infract and neurological dysfunction and promoted apoptosis in IR mice.In conclusion,RW combined with IP reduces brain infract and neurological dysfunction in mice after IR,and this is associated with enhanced anti-apoptotic and anti-oxidant benefits via the activation of PI3K and STAT3 pathways.

Influences of ischemic postconditioning at different positions on oxidative stress of myocardial ischemia-reperfusion injury in rats

Objective:To analyze the influences of locial ischemic postconditioning and remote limb ischemic postconditioning on oxidative stress response with myocardial ischemia reperfusion in rats.Methods:Thirty-two SD rats were randomly divided into Sham group,ischemia/reperfusion(I/R)group,local ischemic postconditioning(LIPC)group,and remote limb ischemic postconditioning(RIPC)group,after 3 hourse reperfusion,the contents of serum creatinine kinase,MB isoenzyme(CK-MB),xanthine oxidase(XOD),superoxide dismutase(SOD),myeloperoxidase(MPO),tumor necrosis factor-α(TNF-α)were measured.The 2,3,5-triphenyltetrazolium chloride(TTC)staining was carried out to evaluate the area of myocardial infarction,cardiac function was evaluated by echocardiography,and HE staining was performed to observe the morphology of myocardial cells.Results:Compared with the Sham group,the SOD contents of the I/R group,LIPC group,RIPC group reduced significantly(P<0.05),the XOD,MPO,TNF-αcontents increased significantly(P<0.05);Compared with the I/R group,the TNF-αcontents of the LIPC group reduced significantly(P<0.05),other oxidative stress indicators of the LIPC group had no significant differences;Compared with the I/R group,the MPO and TNF-αcontents reduced(P<0.05),the SOD and XOD contents of the RIPC group had no significant differences;Compared with the LIPC group,the MPO contents reduced(P<0.05)in the RIPC group,other oxidative stress indicators had no significant differences.Compared with the Sham group,myocardial infarction area,CK-MB contents,LVIDs increased with the reduction of EF in I/R group,LIPC group,RIPC group(P<0.05),HE staining had differences;Compared with the I/R group,myocardial infarction area,CK-MB contents,LVIDd,LVIDs,EF and HE staining results had no significant differences in the LIPC group and the RIPC group;Compared with the RIPC group,the LIPC group had no significant differences.Conclusion:Remote limb ischemic postconditioning and local ischemic postconditioning can partially reduce the oxidative stress response,but does not significantly reduce myocardial infarction area,improve cardiac function.

Evaluation of the effect of hydrogen sulfide postconditioning by p-v loop against myocardial i/r injury in rats

Objectives To evaluate the effect of hydrogen sulfide(H2S) postconditioning on myocardial ischemia-reperfusion (I/R) by pressure-volume loop(P-V loop). Methods The I/R model of rat in vivo was established by ligating the left anterior descending coronary artery for 30min and reperfusing for 120 min.Wistar rats(n=32) were ran- domly divided into 4 groups;Sham operation,ischemia-reperfusion (I/R),Ischemic postconditioning(IPO) and H2S postconditioning.In sham operation,there was no ligation.In IPO,at the start of reperfusion,three cycles of 30s reperfusion and 30s LAD reocclusion preceded the 3h of reperfusion. In H2S postconditioning,NaHS(15μmol/kg,Sodium hydrosulfide)was administrated before coronary artery reperfusion. The heart rate(HR),I/R arrhythmia,the left ventricular end-systolic pressure(LVESP),left ventricular enddiastolic pressure(LVEDP),the slope of the end- systolic P-V relation(ESPVR) and the slope of the end-diastolic P-V relation(EDPVR) were detected.Infarct size was determined by scanning the images of the rat heart ventricular sections stained with Evans blue and TTC.Results Compared with I/R group,the I/R arrhythmia and the infarct size were decreased significantly(PPP2S postconditioning group.Conclusions Myocardial I/R injury was decreased by H2S post-conditioning, and it was sensitive and accurate to evaluate the heart function by P-V loop.