The Protective Effect And Mechanisms Of Endogenous Hydrogen Sulfide On Cerebral Ischemia-reperfusion Injury

Objective: To investigate the protective effect of endogenous hydrogen sulfide (H2S)on ischemia-reperfusion injury and explore the possible mechanisms in the focalcerebral ischemia-reperfused rats.Methods: Fifty SD male rats were randomly divided into the sham control,ischemia-reperfusion model,10μmol/kg,50μmol/kg and100μmol/kg H2S donatorsodium hydrosulfide (NaHS) groups,10rats in each group. NaHS was administered byperitoneal injection30minutes before reperfusion. The rats in sham control,ischemia-reperfusion model group were administered with normal saline. At6h,12h,24h,48h,and72h after the reperfusion, behavioral test was carried out to evaluatethe neurological deficiency. The rats were put to death after reperfusion72h, The2,3,5-three phenyl tetrazolium chloride dye was used to calculate the volume and therate of cerebral infarction. The homogenate of brain tissues in the surrounding area ofischemia was prepared. The level of reactive oxygen species (ROS), the level ofmalondialdehyde (MDA) and the activity of superoxide dismutase (SOD) in the tissuehomogenate of brain tissue were measured by spectrophotography. The level of totalantioxidant capacity (T-AOC) in the tissue homogenate of brain tissue was tested bydouble antibody sandwich assay. The level of reduced glutathione hormon (GSH) in thetissue homogenate of brain tissue was measured by ELISA assay. The mRNA andprotein expressions of BDNF and TrkB of brain tissue in the surrounding area ofischemia were measured by Real-time PCR and Western blot respectively.Results:1．Compared with the ischemia-reperfusion group, the neural function defect was significantly improved, muscle strength was significantly enhanced and the score ofneural function defect was significantly decreased in a dose dependent manner in theNaHS (50and100μmol/Kg) group (all P﹤0.05).2．Compared with the sham group, the concentration of H2S of the tissuehomogenate of brain tissue in the surrounding area of ischemia was significantlydecreased in the ischemia-reperfusion group. Compared with the ischemia-reperfusiongroup, the concentration of H2S of the tissue homogenate of brain tissue in thesurrounding area of ischemia was significantly increased in the NaHS (50and100μmol/Kg) group (all P﹤0.05).3．Compared with the ischemia-reperfusion group, the volume and rate of infarctwere significantly decreased in a dose dependent manner in the NaHS (50and100μmol/Kg) group (all P﹤0.05).4．Compared with the ischemia-reperfusion group, the level of ROS and the levelof MDA in the tissue homogenate of brain tissue in the surrounding area of ischemiawere significantly decreased in a dose dependent manner in the NaHS (50and100μmol/Kg) group (all P﹤0.05); the activity of SOD, the level of T-AOC and the level ofGSH in the tissue homogenate of brain tissue in the surrounding area of ischemia weresignificantly increased in a dose dependent manner in the NaHS (50and100μmol/Kg)group (all P﹤0.05).5． Compared with the ischemia-reperfusion group, the mRNA and proteinexpressions of BDNF and TrkB of brain tissue in the surrounding area of ischemia weresignificantly up-regulated in a dose dependent manner in the NaHS (50and100μmol/Kg) group (all P﹤0.05).Conclusion: Exogenous H2S prevents the ischemia-reperfusion injury in the focalcerebral isehemia-reperfused rats, and its mechanisms may be associated with theinhibition of oxidative stress and up-regulation of BDNF and TrkB induced byexogenous H2S.