Interaction Between Endogenous Hydrogen Sulfide and Nitric Oxide during Rat Global Cerebral Ischemic-Reperfusion

Objective To investigate the interaction between CBS/H2S and iNOS/NO systems during global cerebral ischemia-reperfusion and explore brain protection methods.Methods Twenty-four Wistar male rats were randomly divided into 4 groups(n=6 in each gorup):control(C)group,ischemia-reperfusion(I/R) group,ischemia-reperfusion+aminoguanidine(I/R+A)group,and ischemia-reperfusion+hydroxylamine(I/R+H) group.Global cerebral ischemia-reperfusion model was established by 4-vessel occlusion.The rats in group C were carried out sham operation.The rats in group I/R+A and group I/R+H were respectively intraperitoneal injected 500 mg/kg Aminoguanidine or 5 mmol/L Hydroxylamine before 30 min of clasping bilateral carotid artery.The rats in group C and group I/R were injected equation saline.The carotid clasps were removed after 20 min of 4-vessle occlusion and rats were killed at 6 h after reperfusion.The concentration of H2S,NO,GSH,MDA,the activity of SOD,and expression level of CBS-mRNA and iNOS-mRNA in rats' hippocampus were measured.The mitochondrial structure was observed by electron microscope.Results The concentration of H2S,NO and MDA was increased,GSH and SOD was decreased,iNOS-mRNA and CBS-mRNA expression was increased in group I/R as compared with group C(P0.01).Meanwhile the structure of mitochondrial was destroyed.The levels of NO and MDA were decreased,but H2S,GSH and SOD were increased,iNOS-mRNA expression was decreased and CBS-mRNA was increased in group I/R+A as compared with group I/R(P0.05 or P0.01),meanwhile the injury of mitochondria was alleviated.The levels of GSH and SOD were significantly decreased,but levels of NO and MDA were increased,iNOS-mRNA expression was increased and CBS-mRNA was decreased in group I/R+H as compared with group I/R(P0.05 or P0.01),meanwhile the injury of mitochondria was aggravated.Conclusions iNOS/NO system can induce nerve cells damage,but CBS/H2S has an ahti-damage role in cerebral ischemia-reperfusion,they may interact with each other.iNOS inhibitor has neuroprotective effects.