Study On The Changes Of Expression And Activity Levels Of Caspase3 As Well As The Effect Of Caspase3 Inhibitor On Survival And Apoptosis Of Neurons In Penumbra

Ischemic cerebral vascular disease is still a serious disease which threats human health and life quality. Now it is generally agreed that apoptosis is the chief death pattern of neurons in penumbra after ischemia and reperfusion injury of brain. During apoptosis progress, firstly, caspaseS is activated by proteolysis as two fiagments. Then, poly(ADP-ribose)polymerase(PARP), a 116 KDa DNA repairing enzyme , served as CaspaseS's substrate, is cleaved in a 89KDa C -fiagment and a 24KDa N -fragment. This is the definit characterization of apoptosis. hi present study, apoptosis degree was observed by TUNEL as well as changes of expression and activity levels of Caspase3, and expression and cleavage of PARP in penumbra were detected the used rat model of middle cerebral artery filament occlusion and reperfusion (MCAO), Western Blotting and immunohistochemistry. Besides, we also investigated the protecting effect of z-DEVD.fink, a caspaseS inhibitor, on the neurons in penumbra. At the same time, we detected GFAP positive cells density by immunohistochemistry which is a indicator of astrocytes ischemic injury. Especially, we analysed the correlation among above parameters one another. The results showed that , as a function of time intervals , the levels of expression and activity of CaspaseS, and quantities of expression and cleavage of PARP increased after MCAO, in concordance with the deterioration of apoptosis. After using z-DEVD.fink, the activity of CaspaseS and cleavage of PARP were decreased, but the expression were still increased The results were consistent with our previous expectation and suggested that caspaseS inhibitor could effectively protecte ischemic neurons and astrocytes and prevent them from apoptosis. We have not observed astrocytes injury before neurons pathological changes after cerebral ischemia.