HSP110 aggravates ischemia-reperfusion injury after liver transplantation by promoting NF-κB pathway

Background:Ischemia-reperfusion injury(IRI)poses a significant challenge to liver transplantation(LT).The underlying mechanism primarily involves overactivation of the immune system.Heat shock protein 110(HSP110)functions as a molecular chaperone that helps stabilize protein structures.Methods:An IRI model was established by performing LT on Sprague-Dawley rats,and HSP110 was silenced using siRNA.Hematoxylin-eosin staining,TUNEL,immunohistochemistry,ELISA and liver enzyme analysis were performed to assess IRI following LT.Western blotting and quantitative reverse transcription-polymerase chain reaction were conducted to investigate the pertinent molecular changes.Results:Our findings revealed a significant increase in the expression of HSP110 at both the mRNA and protein levels in the rat liver following LT(P<0.05).However,when rats were injected with siRNAHSP110,IRI subsequent to LT was notably reduced(P<0.05).Additionally,the levels of liver enzymes and inflammatory chemokines in rat serum were significantly reduced(P<0.05).Silencing HSP110 with siRNA resulted in a marked decrease in M1-type polarization of Kupffer cells in the liver and downregulated the NF-κB pathway in the liver(P<0.05).Conclusions:HSP110 in the liver promotes IRI after LT in rats by activating the NF-κB pathway and inducing M1-type polarization of Kupffer cells.Targeting HSP110 to prevent IRI after LT may represent a promising new approach for the treatment of LT-associated IRI.

Polydatin ameliorates hepatic ischemia-reperfusion injury by modulating macrophage polarization

Background:Polydatin,a glucoside of resveratrol,has shown protective effects against various diseases.However,little is known about its effect on hepatic ischemia-reperfusion(I/R)injury.This study aimed to elucidate whether polydatin protects liver against I/R-induced injury and to explore the underlying mechanism.Methods:After gavage feeding polydatin once daily for a week,mice underwent a partial hepatic I/R procedure.Serum alanine aminotransferase(ALT)/aspartate aminotransferase(AST),hematoxylin-eosin(H&E)and TdT-mediated dUTP nick-end labeling(TUNEL)staining were used to evaluate liver injury.The severity related to the inflammatory response and reactive oxygen species(ROS)production was also investigated.Furthermore,immunofluorescence and Western blotting were used to detect macrophage polarization and the NF-κB signaling pathway in macrophages.Results:Compared with the I/R group,polydatin pretreatment significantly attenuated I/R-induced liver damage and apoptosis.The oxidative stress marker(dihydroethidium fluorescence,malondialdehyde,superoxide dismutase and glutathione peroxidase)and I/R related inflammatory cytokines(interleukin1β,interleukin-10 and tumor necrosis factor-α)were significantly suppressed after polydatin treatment.In addition,the result of immunofluorescence indicated that polydatin reduced the polarization of macrophages toward M1 macrophages both in vivo and in vitro.Western blotting showed that polydatin inhibited the pro-inflammatory function of RAW264.7 via down-regulating the NF-κB signaling pathway.Conclusions:Polydatin protects the liver from I/R injury by remodeling macrophage polarization via NFκB signaling.

Combining neural progenitor cell transplant and rehabilitation for enhanced recovery after cervical spinal cord injury

Efforts to promote recovery of function after human spinal cord injury(SCI) will likely require interventions to rgeting the corticospinal tract(CST) motor system:the most important pathway for voluntary motor control in humans.This system has historically been the most refractory to regenerative efforts after SCI.The "nonregeneration" of the CST changed when robust regeneration of the CST into spared tissue was demonstrated by the inactivation of phosphatase and tensin homolog and delivery of inosine.

Inhibition of the cGAS–STING pathway:contributing to the treatment of cerebral ischemia-reperfusion injury

The cGAS–STING pathway plays an important role in ischemia-reperfusion injury in the heart,liver,brain,and kidney,but its role and mechanisms in cerebral ischemia-reperfusion injury have not been systematically reviewed.Here,we outline the components of the cGAS–STING pathway and then analyze its role in autophagy,ferroptosis,cellular pyroptosis,disequilibrium of calcium homeostasis,inflammatory responses,disruption of the blood–brain barrier,microglia transformation,and complement system activation following cerebral ischemia-reperfusion injury.We further analyze the value of cGAS–STING pathway inhibitors in the treatment of cerebral ischemia-reperfusion injury and conclude that the pathway can regulate cerebral ischemia-reperfusion injury through multiple mechanisms.Inhibition of the cGAS–STING pathway may be helpful in the treatment of cerebral ischemia-reperfusion injury.

Network pharmacology investigation of the mechanism underlying the therapeutic action of Shikang granules in retinal ischemia-reperfusion injuries

Background:Retinal ischemia/reperfusion(I/R)injury often results in vision loss,and effective clinical management options are currently lacking.Shikang granules(SKG)are traditional Chinese medicine-based preparations commonly used in clinical practice for treating optic atrophy.Methods:Despite decades of clinical use,the precise mechanism of action(MoA)of SKG remains elusive.Here,we employ a network pharmacological approach to elucidate its MoA by identifying active ingredients and relevant targets using the Traditional Chinese Medicine System Pharmacology Database and Analytical Platform.Targets associated with retinal I/R injury were sourced from GeneCards,Online Mendelian Inheritance in Man,and DisGeNET.Venny software facilitated the identification of intersecting targets,which were then subjected to gene ontology functional analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis.To validate the protective effect and explore the MoA of SKG in retinal I/R injuries,we conducted experiments using rat models.Results:Our animal experiments demonstrated that SKG mitigated apoptosis following retinal I/R injury by upregulating the expression of the anti-apoptotic protein Bcl-2 and downregulating the expression of BAX,Caspase-9,Caspase-3,PARP,and cytochrome C.Additionally,SKG was found to increase the expression of PI3K and AKT.Conclusions:SKG may exert its protective effects by inhibiting apoptosis through modulation of pro-apoptotic and anti-apoptotic protein expression,as well as activation of the PI3K/AKT pathway.

Research progress of lncRNA and miRNA in hepatic ischemia-reperfusion injury

Background:Hepatic ischemia-reperfusion injury(HIRI)is a common complication of liver surgeries,such as hepatectomy and liver transplantation.In recent years,several non-coding RNAs(nc RNAs)including long non-coding RNAs(lnc RNAs)and micro RNAs(mi RNAs)have been identified as factors involved in the pathological progression of HIRI.In this review,we summarized the latest research on lnc RNAs,mi RNAs and the lnc RNA-mi RNA regulatory networks in HIRI.Data sources:The Pub Med and Web of Science databases were searched for articles published up to December 2021 using the following keywords:“hepatic ischemia-reperfusion injury”,“lnc RNA”,“long noncoding RNA”,“mi RNA”and“micro RNA”.The bibliography of the selected articles was manually screened to identify additional studies.Results:The mechanism of HIRI is complex,and involves multiple lnc RNAs and mi RNAs.The roles of lnc RNAs such as AK139328,CCAT1,MALAT1,TUG1 and NEAT1 have been established in HIRI.In addition,numerous mi RNAs are associated with apoptosis,autophagy,oxidative stress and cellular inflammation that accompany HIRI pathogenesis.Based on the literature,we conclude that four lnc RNA-mi RNA regulatory networks mediate the pathological progression of HIRI.Furthermore,the expression levels of some lnc RNAs and mi RNAs undergo significant changes during the progression of HIRI,and thus are potential prognostic markers and therapeutic targets.Conclusions:Complex lnc RNA-mi RNA-m RNA networks regulate HIRI progression through mutual activation and antagonism.It is necessary to screen for more HIRI-associated lnc RNAs and mi RNAs in order to identify novel therapeutic targets.

Peripheral blood RNA biomarkers can predict lesion severity in degenerative cervical myelopathy

Degenerative cervical myelopathy is a common cause of spinal cord injury,with longer symptom duration and higher myelopathy severity indicating a worse prognosis.While numerous studies have investigated serological biomarkers for acute spinal cord injury,few studies have explored such biomarkers for diagnosing degenerative cervical myelopathy.This study involved 30 patients with degenerative cervical myelopathy(51.3±7.3 years old,12 women and 18 men),seven healthy controls(25.7±1.7 years old,one woman and six men),and nine patients with cervical spondylotic radiculopathy(51.9±8.6 years old,three women and six men).Analysis of blood samples from the three groups showed clear differences in transcriptomic characteristics.Enrichment analysis identified 128 differentially expressed genes that were enriched in patients with neurological disabilities.Using least absolute shrinkage and selection operator analysis,we constructed a five-gene model(TBCD,TPM2,PNKD,EIF4G2,and AP5Z1)to diagnose degenerative cervical myelopathy with an accuracy of 93.5%.One-gene models(TCAP and SDHA)identified mild and severe degenerative cervical myelopathy with accuracies of 83.3%and 76.7%,respectively.Signatures of two immune cell types(memory B cells and memory-activated CD4^(+)T cells)predicted levels of lesions in degenerative cervical myelopathy with 80%accuracy.Our results suggest that peripheral blood RNA biomarkers could be used to predict lesion severity in degenerative cervical myelopathy.

Liqi Huoxue dripping pill protects against myocardial ischemia-reperfusion injury via the PI3K/Akt/GSK-3β signaling pathway in rats

Background:Liqi Huoxue dripping pill(LQHXDP),a traditional Chinese drug for coronary heart disease,has a protective effect on the heart of rats with myocardial ischemia-reperfusion injury(MIRI)in previous studies;however,its mechanism of action remains unclear.The purpose of this study was to investigate the protective mechanism of LQHXDP on MIRI in rats and its relationship with the PI3K/Akt signaling pathway.Methods:In this study,Sprague-Dawley rats were pre-infused with LQHXDP(175 mg/kg/d)for 10 days.PI3K inhibitor LY294002(0.3 mg/kg)was intravenously injected 15 minutes before ischemia.The rat model of MIRI was established by ligating the left anterior descending coronary artery.Subsequently,cardiac hemodynamics,serum myocardial injury markers,inflammatory factors,myocardial infarct size,antioxidant indexes,myocardial histopathology,and phosphorylation levels of key proteins of PI3K/Akt signaling pathway were assessed in rats.Results:LQHXDP was found to improve cardiac hemodynamic indexes,reduce serum creatine kinase MB isoenzyme activity and cardiac troponin and heart-type fatty acid binding protein levels,lower serum interleukin-1 beta,interleukin-6 and tumour necrosis factorαlevels,reduce the myocardial infarct size and enhance the antioxidant capacity of myocardial tissue in MIRI rats.Pathological analysis revealed that LQHXDP attenuated the extent of myocardial injury and protected mitochondria from damage in MIRI rats.Immunoblot analysis revealed that LQHXDP increased the expression levels of p-Akt and p-GSK-3βin MIRI rat cardiomyocytes.PI3K inhibitor LY294002 could impair these effects of LQHXDP.Conclusion:LQHXDP attenuated myocardial injury,attenuated oxidative stress injury and reduced inflammatory response in MIRI rats,and its protective effects were mediated by activating of PI3K/Akt/GSK-3βsignaling pathway.

Protective effects of combined treatment with ciprofol and mild therapeutic hypothermia during cerebral ischemia-reperfusion injury

Despite improvement in cardiopulmonary resuscitation(CPR)performance,cardiac arrest(CA)is still associated with poor prognosis.The high mortality rate is due to multi-organ dysfunction caused by cerebral ischemia and reperfusion injury(I/R).The guidelines for CPR suggest the use of therapeutic hypothermia(TH)as an effective treatment to decrease mortality and the only approach confirmed to reduce I/R injury.During TH,sedative agents(propofol)and analgesia agents(fentanyl)are commonly used to prevent shiver and pain.However,propofol has been associated with a number of serious adverse effects such as metabolic acidosis,cardiac asystole,myocardial failure,and death.In addition,mild TH alters the pharmacokinetics of agents(propofol and fentanyl)and reduces their systemic clearance.For CA patients undergoing TH,propofol can be overdosed,leading to delayed awakening,prolonged mechanical ventilation,and other subsequent complications.Ciprofol(HSK3486)is a novel anesthetic agent that is convenient and easy to administer intravenously outside the operating room.Ciprofol is rapidly metabolized and accumulates at low concentrations after continuous infusion in a stable circulatory system compared to propofol.Therefore,we hypothesized that treatment with HSK3486 and mild TH after CA could protect the brain and other organs.

Non-coding RNAs:The potential biomarker or therapeutic target in hepatic ischemia-reperfusion injury

Hepatic ischemia-reperfusion injury(HIRI)is the major complication of liver surgery and liver transplantation,that may increase the postoperative morbidity,mortality,tumor progression,and metastasis.The underlying mechanisms have been extensively investigated in recent years.Among these,oxidative stress,inflammatory responses,immunoreactions,and cell death are the most studied.Non-coding RNAs(ncRNAs)are defined as the RNAs that do not encode proteins,but can regulate gene expressions.In recent years,ncRNAs have emerged as research hotspots for various diseases.During the progression of HIRI,ncRNAs are differentially expressed,while these dysregulations of ncRNAs,in turn,have been verified to be related to the above pathological processes involved in HIRI.ncRNAs mainly contain microRNAs,long ncRNAs,and circular RNAs,some of which have been reported as biomarkers for early diagnosis or assessment of liver damage severity,and as therapeutic targets to attenuate HIRI.Here,we briefly summarize the common pathophysiology of HIRI,describe the current knowledge of ncRNAs involved in HIRI in animal and human studies,and discuss the potential of ncRNA-targeted therapeutic strategies.Given the scarcity of clinical trials,there is still a long way to go from pre-clinical to clinical application,and further studies are needed to uncover their potential as therapeutic targets.

Effect of salvianolic acid B-loaded mesoporous silica nanoparticles on myocardial ischemia-reperfusion injury

Background:Currently,no drugs can specifically improve clinical cardiac ischemia-reperfusion injury or the prognosis of hemodialysis.Salvianolic acid B(SalB)is a widely used cardiac protectant;however,its clinical application is limited by its low oral bioavailability and poor intestinal absorption.The exploration of its preparation and clinical applications has become a research hotspot in recent years.Methods:To determine whether mesoporous silica nanoparticles(MSNs)efficiently delivered SalB to the heart and SalB@MSNs-RhB reduced myocardial ischemia-reperfusion injury,we constructed a myocardial ischemia-reperfusion male rat model,hypoxia/reoxygenation cardiomyocytes,and treated them with SalB@MSNs-RhB.Results:SalB@MSNs-RhB showed improved bioavailability,therapeutic effect,heightened JAK2/STAT3-dependent pro-survival signaling,and antioxidant responses,thereby protecting cardiomyocytes from ischemia-reperfusion injury-induced oxidative stress and apoptosis.Conclusion:This use of SalB-loaded nanoparticles and investigation of their mechanism of action may provide a new strategy for treating cardiomyocytes.Thus,hypoxia/reoxygenation promotes the clinical application of SalB.

Selection of Surgical Approach and Clinical Significance of Lower Cervical Spine Injuries Guided by SLIC Scoring System

Objective: To explore the feasibility and clinical significance of surgical approach selection for cervical spine injury guided by SLIC scoring system. Methods: The clinical data of 75 patients with lower cervical injury surgery from January 2020 to November 2022 were retrospectively analyzed, including 48 males and 27 females. Age: 28 - 65 years old. Causes of injury: 39 cases of traffic accidents, 15 cases of ice and snow sports, 12 cases of falling from high places, 9 cases of heavy objects. There were 12 cases of C3-4, 33 cases of C4-5, 21 cases of C5-6, and 9 cases of C6-7. Time from injury to medical treatment: 4 h - 2 d. Cervical spine X-ray, MRI, MDCT examination and preoperative SLIC score were performed on admission. Anterior approach was performed by subtotal cervical vertebrae resection or discectomy, titanium Cage or cage supported bone grafting and anterior titanium plate fixation. Posterior approach was performed with cervical laminoplasty, lateral mass or pedicle screw fixation and fusion. The combined anterior-posterior operation was performed by the anterior methods+ posterior methods. The time from injury to surgery is 12 h to 3 d. The function before and after operation was evaluated by JOA efficacy evaluation criteria. The correlation between the three surgical approaches and postoperative efficacy and SLIC score was compared. SPSS 22.0 software was used for statistical analysis of the data. Results: In this group of 75 patients, 32 cases of anterior operation, 22 cases of posterior operation and 21 cases of combined operation were followed up for no less than 12 months. There was no significant difference in age, gender, injury cause, injury segment, time from injury to treatment, and time from injury to operation among the three surgical approaches, which were comparable. The SLIC scores of mild, moderate and severe injuries of anterior surgery, posterior surgery and combined anterior and posterior surgery, They were (5.26 ± 1.24, 5.86 ± 1.67, 8.25 ± 0.21), (5.57 ± 1.43, 5.99 ± 1.85, 9.00 ± 0.25), (0, 5.98 ± 0.33, 9.44 ± 0.34), respectively. By comparing the SLIC scores and JOA scores of anterior surgery and posterior surgery, there was no difference in SLIC scores and JOA scores between the two groups for mild and moderate injuries (P > 0.05). However, the JOA scores at 3 months, 6 months and 12 months after surgery were different from those before surgery, and the postoperative efficacy and JOA scores were significantly improved (P & lt;0.05), indicating that the two surgical methods had the same therapeutic effect, that is, anterior or posterior surgery could be used to treat mild or moderate injuries (P > 0.05). There were differences in SLIC scores among the three surgical approaches for severe injury (P 0.05). The postoperative efficacy and JOA score of combined anterior-posterior approach were significantly improved compared with those before operation (P Conclusion: SLIC score not only provides accurate judgment for conservative treatment or surgical treatment of cervical spine injury, but also provides evidence-based medical basis and reference value for the selection of surgical approach and surgical method. According to the SLIC score, the surgical approach is safe and feasible. When the SLIC score is 4 - 7, anterior surgery is selected for type A injury, and posterior surgery is selected for type B injury. When the SLIC score is ≥8, combined anterior-posterior surgery should be selected. It is of great significance for clinical formulation of precision treatment strategy.

Atorvastatin Alleviates Myocardial Ischemia-Reperfusion Injury via miR-26a-5p/FOXO1

Purpose: Ischemia-reperfusion (I/R) injury exacerbates myocardial cell death (including apoptosis and necrosis), leading to complications such as arrhythmias, myocardial stenosis, microvascular obstruction and heart failure, and it is particularly important to seek new strategies to mitigate reperfusion injury. In this paper, we will investigate whether atorvastatin can alleviate myocardial ischemia-reperfusion injury and verify its molecular mechanism. Methods: We successfully constructed a hypoxia-reperfusion (H/R) H9c2 cell model and transfected miR-26a-5p mimic, miR-26a-5p inhibitor and its negative control NC-mimic or NC-inhibitor into H9c2 cells using a transfection kit. The expression of miR-26a-5p and FOXO1 were detected by RT-qPCR assay, the expression of related proteins by Western blot assay, the cell viability of H9c2 cells by CCK-8 assay, the apoptosis rate of H9c2 cells by flow cytometry, the CK and LDH activity in cells by CK and LDH assay kits. The targeting relationship between miR-26a-5p and FOXO1 was verified by dual luciferase reporter gene assay. Results: MiR-26a-5p expression was decreased in H/R-induced cells and FOXO1 expression was increased in H/R-induced cells. Atorvastatin alleviated H/R injury in cardiomyocytes and was most effective at a concentration of 1 μM. Atorvastatin alleviated H/R injury in cardiomyocytes by upregulating miR-26a-5p expression, miR-26a-5p and FOXO1 were negatively regulated by targeting. Conclusion: Atorvastatin can alleviate H/R injury in cardiomyocytes by regulating miR-26a-5p/FOXO1.

Improved methodology for efficient establishment of the myocardial ischemia-reperfusion model in pigs through the median thoracic incision

To investigate the feasibility and effectiveness of establishing porcine ischemia-reperfusion models by ligating the left anterior descending(LAD)coronary artery,we first randomly divided 16 male Bama pigs into a sham group and a model group.After anesthesia,we separated the arteries and veins.Subsequently,we rapidly located the LAD coronary artery at the beginning of its first diagonal branch through a mid-chest incision.Then,we loosened and released the ligation line after five minutes of pre-occlusion.Finally,we ligated the LAD coronary artery in situ two minutes later and loosened the ligature 60 min after ischemia.Compared with the sham group,electrocardiogram showed multiple continuous lead ST-segment elevations,and ultrasound cardiogram showed significantly lower ejection fraction and left ventricular fractional shortening at one hour and seven days post-operation in the model group.Twenty-four hours after the operation,cardiac troponin T and creatine kinase-MB isoenzyme levels significantly increased in the model group,compared with the sham group.Hematoxylin and eosin staining showed the presence of many inflammatory cells infiltrating the interstitium of the myocardium in the model group but not in the sham group.Masson staining revealed a significant increase in infarct size in the ischemia/reperfusion group.All eight pigs in the model group recovered with normal sinus heart rates,and the survival rate was 100%.In conclusion,the method can provide an accurate and stable large animal model for preclinical research on ischemia/reperfusion with a high success rate and homogeneity of the myocardial infarction area.

Heat shock pretreatment improves stem cell repair following ischemia-reperfusion injury via autophagy

AIM: To investigate whether heat shock pretreatment(HSP) improves mesenchymal stem cell(MSC) repair via autophagy following hepatic ischemia-reperfusion injury(HIRI).METHODS: Apoptosis of MSCs was induced by 250 m M hydrogen peroxide(H2O2) for 6 h. HSP was carried out using a 42 ℃ water bath for 1, 2 or 3 h. Apoptosis of MSCs was analyzed by flow cytometry, and Western blot was used to detect Bcl-2, Bax and cytochrome C expression. Autophagy of MSCs was analyzed by flow cytometry and transmission electron microscopy, and the expression of beclin Ⅰ?and LC3-Ⅱ was detected by Western blot. MSCs were labeled in vivo with the fluorescent dye, CM-Dil, and subsequently transplanted into the portal veins of rats that had undergone HIRI. Liver levels of proliferating cell nuclear antigen(PCNA) were quantified by fluorescent microscopy. Serum aminotransferase activity and the extent of HIRI were also assessed at each time point.RESULTS: HSP for 2 h reduced apoptosis of MSCs induced by H2O2 as seen by a decrease in apoptotic rate, a decrease in Bax and cytochrome C expression and an increase in Bcl-2 expression(P < 0.001). In addition, HSP for 2 h induced autophagy of MSCs exposed to H2O2 as shown by an increase in acidic vesicular organelle-positive cells, beclin 1 and LC3-Ⅱ expression, and autophagosome formation(P < 0.05). Treatment with 3-methyladenine attenuated HSPinduced autophagy and abolished the protective effects of HSP on the apoptosis of MSCs. Rapamycin failed to have additional effects on either autophagy or apoptosis compared with HSP alone. The phosphorylation of p38 MAPK was significantly elevated and the phosphorylation of m TOR was downregulated in heat shock pretreated MSCs. Treatment with the p38 MAPK inhibitor, SB203580, reduced HSP-induced autophagy in MSCs. In vivo studies showed that the transplantation of HSP-MSCs resulted in lower serum aminotransferase levels, lower Suzuki scores, improved histopathology and an increase in PCNA-positive cells(P < 0.05).CONCLUSION: HSP effectively induces autophagy following exposure to H2O2 via the p38MAPK/m TOR pathway, which leads to enhanced MSC survival and improved MSC repair following HIRI in rats.

The role and modulation of autophagy in experimental models of myocardial ischemia-reperfusion injury

A physiological sequence called autophagy qualitatively determines cellular viability by removing protein aggregates and damaged cyto-plasmic constituents, and contributes significantly to the degree of myocardial ischemia-reperfusion （I/R） injury. This tightly orchestrated cata-bolic cellular‘housekeeping’ process provides cells with a new source of energy to adapt to stressful conditions. This process was first described as a pro-survival mechanism, but increasing evidence suggests that it can also lead to the demise of the cell. Autophagy has been implicated in the pathogenesis of multiple cardiac conditions including myocardial I/R injury. However, a debate persists as to whether autophagy acts as a protec-tive mechanism or contributes to the injurious effects of I/R injury in the heart. This controversy may stem from several factors including the va-riability in the experimental models and species, and the methodology used to assess autophagy. This review provides updated knowledge on the modulation and role of autophagy in isolated cardiac cells subjected to I/R, and the growing interest towards manipulating autophagy to increase the survival of cardiac myocytes under conditions of stress-most notably being I/R injury. Perturbation of this evolutionarily conserved intracellular cleansing autophagy mechanism, by targeted modulation through, among others, mammalian target of rapamycin （mTOR） inhibitors, adenosine monophosphate-activated protein kinase （AMPK） modulators, calcium lowering agents, resveratrol, longevinex, sirtuin activators, the proapoptotic gene Bnip3, IP3 and lysosome inhibitors, may confer resistance to heart cells against I/R induced cell death. Thus, therapeutic ma-nipulation of autophagy in the challenged myocardium may benefit post-infarction cardiac healing and remodeling.

Mechanisms of hepatic ischemia-reperfusion injury and protective effects of nitric oxide

Hepatic ischemia-reperfusion injury(IRI) is a patho-physiological event post liver surgery or transplantation and significantly influences the prognosis of liver func-tion. The mechanisms of IRI remain unclear, and effec-tive methods are lacking for the prevention and therapy of IRI. Several factors/pathways have been implicated in the hepatic IRI process, including anaerobic metabo-lism, mitochondria, oxidative stress, intracellular cal-cium overload, liver Kupffer cells and neutrophils, and cytokines and chemokines. The role of nitric oxide(NO)in protecting against liver IRI has recently been report-ed. NO has been found to attenuate liver IRI through various mechanisms including reducing hepatocellular apoptosis, decreasing oxidative stress and leukocyte adhesion, increasing microcirculatory flow, and enhanc-ing mitochondrial function. The purpose of this review is to provide insights into the mechanisms of liver IRI, indicating the potential protective factors/pathways that may help to improve therapeutic regimens for control-ling hepatic IRI during liver surgery, and the potential therapeutic role of NO in liver IRI.

Role of nitric oxide in hepatic ischemia-reperfusion injury

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.

Heme oxygenase system in hepatic ischemia-reperfusion injury

Hepatic ischemia-reperfusion injury (IRI) limits access to transplantation. Heme oxygenase-1 (HO-1) is a powerful antioxidant enzyme which degrades free heme into biliverdin,free iron and carbon monoxide. HO-1 and its metabolites have the ability to modulate a wide variety of inflammatory disorders including hepatic IRI. Mechanisms of this protective effect include reduction of oxygen free radicals,alteration of macrophage and T cell phenotype. Further work is required to understand the physiological importance of the many actions of HO-1 identified experimentally,and to harness the protective effect of HO-1 for therapeutic potential.

Protection Against Hepatic Ischemia-reperfusion Injury in Rats by Oral Pretreatment With Quercetin

Objective To investigate the possible protection provided by oral quercetin pretreatment against hepatic ischemia-reperfusion injury in rats. Methods The quercetin （0.13 mmol/kg） was orally administrated in 50 min prior to hepatic ischemia-reperfusion injury. Ascorbic acid was also similarly administered. The hepatic content of quercetin was assayed by high performance liquid chromatography （HPLC）. Plasma glutamic pyruvic transaminase （GPT）, glutamic oxaloacetic transaminase （GOT） activities and malondialdehyde （MDA） concentration were measured as markers of hepatic ischemia-reperfusion injury. Meanwhile, hepatic content of glutathione （GSH）, activities of superoxide dismutase （SOD）, glutathione peroxidase （GSH-Px） and xanthine oxidase （XO）, total antioxidant capacity （TAOC）, contents of reactive oxygen species （ROS） and MDA, DNA fragmentation were also determined. Results Hepatic content of quercetin after intragastric administration of quercetin was increased significantly. The increases in plasma GPT