| Ischemic cerebral vascular disease is one of the common disease that threaten human health.The pathophsiological mechanism of ischemic neuronal injury remains unclear,probably involved in many factors such as the releasing of massive glutamate,increasing in intracellular calcium and generation of free radicals.Recent studies indicated that nitric oxide(NO) play an important role in disease of central neurological system and take part in ischemic neuronal damage. peroxynitrite (ONOO-),a product from rapid reaction of NO and superoxide anion(),may be an important mediator for cytotoxicity due to excessive NO generation. ONOO- is a reactive regent which have strong oxidation and nitration.In addition, ONOO- can diffuse across membrane.Experiment in vitro showed that ONOO- induced cleavage of purified DNA strand,membrane lipoperoxide, modefication of protein residues, apoptosis and necrosis in different kinds of cells.High levels of NO and are generated by neurons, microglias,astrocytes and a variety of inflammatory cells including neutrophils,lymphocytes and macrophages.It is seldom reported for production of ONOO- in brain during cerebral ischemia and reperfusion .whether or not ONOO- mediated injury of cerebral ischemia and reperfusion remains to be investigated.NO is synthesized from oxygen and L-arginine with the catalysis of nitric oxide synthase(NOS).NOS include three forms which are neuronal nitric oxide synthase(nNOS),endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase(iNOS).Researches indicated NO from nNOS mediates early cerebral ischemic and reperfusional injury.NO fromeNOS is protective in early cerebral ischemic and reperfusional injury. NO from iNOS contributes to late cerebral ischemic and reperfusional injury.In order to suppress the neurtoxic role of NO and exert its protective role,the selective inhibitor of nNOS,7-nitroindazole,was given at the early stage of cerebral ischemia and reperfusion,while aminoguandine ,a selective iNOS inhibitor,was given at the late stage of cerebral ischemia and reperfusion.Apoptosis is an active form of cell death under the regulation of some genes.The triggering or suppression of apoptosis is depend on the interaction of proapoptotic genes and antiapoptotic genes.More and more evidence suggest that neuronal apoptosis anticipate ischemic cerebral injury,especially play an important role in the delayed neuronal death.Experiment in vitro showed that high concentration of NO/ONOO- caused many kinds of cell apoptosis,but the role NO/ONOO- in cellular apoptosis induced by cerebral ischemia and reperfusion and the related genomic regulation remains unclear.Mitochondrion is an important subcellular organ of cell.Rearches indicate that mitochondrion not only play an important role in triggering and regulating cellular apoptosis, but also a key element of apoptotic execution. The basically biochemical pathway of apoptosis involves mitochondrial permeability transition (mPT) pore opening induced by death signal,mitochondrial membrane potential collapsing,proapoptotic protein releasing and caspases activiting.It is found that there are independent mitochondrial NOS(mtNOS) in mitochondria.Therefore, mitochondria can generate not only but also NO,the two latter rapid react to form ONOO-,which can lead to mitochondrial damage. Determination of the property of mitochondrial reaction will be useful to clarify mechanisms of cerebral ischemic cell death and afford new target for therapy .Therefore,the present study was undertaken to observe the formation and localization of ONOO- and the ultrastructral changes of brain tissue following focal cerebral ischemia and reperfusion in rat.The selective inhibitor of nNOS ,7-NI and the selective inhibitor,AG weregiven to investigate the role and the related mechanism of NO/ ONOO- in tissue injury and cellular apoptosis following cerebral ischemia and reperfusion.The effects of NO on mitochondrial damage caused by exogenous calcium was also observed.The results are as follows:1 Change...
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