Correlation between HSP70 and c-F0S expression and apoptosis in rats undergolng transient focal cerebral ischemla and reperfusion
OBJECTIVE To compare the induction of c-Fos and HSP70 and the presence of apoptosis and the influence of Ginkgo biloba extract (EGb761) in transient focal cerebral ischemic reperfusion rats.BACKGROUND Proto ancogene activation and induction of heat shock protein (HSP) occur in response to cerebral ischemia, but the correlation between these proteins and apoptosis remains uncertain. METHODS Healthy wistar rats were randomized to the normal control group(Group A, n=4), the Sham-operated control group(Group B, n=4), the ischemia and reperfusion group(Group C, n=24), the EGb761 pre-treated ischemia and reperfusion group(Group D, n=24). The rats of Group C and Group D were subjected to transient left middle cerebral artery occlusion (MCAO) as described by Zea longa for 1 hour. RESULTS Immunohistochemical analysis revealed no c-Fos or HSP70-immunoreactivity in Group A and Group B rats. However, in Group C rats, c-Fos was expressed in ipsilateral superficial cortical layers at 1 hour after reperfusion. At 6 hours, c-Fos immunoreactivities were increased in the ipsilateral cortex and were present in the contralateral cortex, while HSP70 were induced beginning in the ipsilateral neurons of MCA distribution. At 12 hours, the expression of c-Fos reached top in superficial cortical layers. At 24 hours HSP70 immunoreactivities reached top both in ipsilateral cortex and in ipsilateral striatum. At 3 days after recirculation, HSP70 expression decreased. c-Fos expression disappeared at day 7 and HSP70 expression only occured in endothelial cells. TUNEL staining showed that there was no cell apoptosis in Gronp A or in Group B. However, in Group C, TUNEL-positive neurons were observed in the border of the penumbra-like area that surrounds the ischemic core at 6 hours following reperfusion and then the number of TUNEL-positive cells reduced gradually. The changes in expression of HSP70 and c-Fos at different time points in Group D was in accord with in Group C, but the number of positive cells and the immunoreactivities in Group D were more intense than in Group C. We found only several TUNEL-positive cells at 6 hours following reperfusion in Group D and no TUNE;L-positive cells were present at other time points.CONCLUSION The present results indicate that c-Fos was expressed from an earlier stage of reperfusion and the expression occured in bilateral cerebral cortex. In contrast, HSP70 induction began later and only occured in ipsilateral neurons of MCA distribution. Our results indicated that EGb761 could increase the expression of c Fos and HSP70 and reduce the apoptosis of neurons.
ischemia and reperfusion、middle cerebral artery、Ginkgo biloba extract、heat shock protein、endothelial cells、cerebral ischemia、cerebral cortex、cell apoptosis、wistar rats
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R5 ;R99
2005-07-07(万方平台首次上网日期,不代表论文的发表时间)
共1页
70