RESUMO
Objective To investigate the expression of GRP78 and caspase-12 on the auditory cortex and to study the effects of endoplasmic reticulum stress in the auditory cortex neuron apoptosis after the brain ischemia reperfusion injury in guinea pig.Methods Fifty healthy male guinea pigs were selected and randomly divided into 5 groups which were hormal group group A(reperfusion for 6 hours),group B(reperfusion for 12 hours),group C (reperfusion for 24 hours),group D(reperfusion for 72 hours).The cerebral ischemia reperfusion injury model was produced by the occlusion of bilateral common carotid arteries.The guinea pigs were sacrificed at reperfusion of 6, 12,24,and 72 hours respectively after they received ABR tests.The pathological changes were observed by HE and the levels of GRP78 and caspase-12 protein were detected by immunohistochemistry and Western blot.Results The hearing thresholds increased gradually from the normal group to group B,and decreased gradually from group C to group D,but the thresholds of group D were still higher than that of the normal group.HE staining showed that the neurons in the normal control group were arranged in order,the cytoplasm was abundant,large and round.The cells were stained clearly.After reperfusion,the number of neurons in each time point was decreased,the nucleus presented atrophic,fragmented,the disappeared.The expression of GRP78 and caspase-12 protein in normal con-trol group was only a trace or a small amount by immunohistochemistry and Western blot.The expression of GRP78 and caspase-12 began to inerease.The expression of GRP78 reached the peak at reperfusion of 12 hours and de-creased gradually.There were significant statistic differences between each group comparison.The expression of caspase-12 reached the peak at reperfusion of 24 hours,then decreased gradually.There was no statistic difference between group A and group B.There were significant statistic differences anong other groups.Conclusion Endo-plasmic reticulum stress(ERS)may be induced by brain ischemia reperfusion injury,and can increase the expression of GRP78 and caspase-12.GRP78 and caspase-12 participate in the process of neuron apoptosis on auditory cor-tex caused by ERS.
RESUMO
Objective To investigate the protective effect of nimodipine on neuron of the rats with focal cerebral ischemia-reperfusion injury and the expressions of Bax and Bcl-2,and to clarify their mechanisms.Methods The focal cerebral-ischemia reperfusion model was induced by the middle cerebral artery occlusion(MCAO)method. 30 male Wistar rats were randomly divided into sham operation,model,and nimodipine groups(n=10).The neurological deficit score was performed after 2 h ischemia following 2 h reperfusion.The infarction was observed by TUNEL staining and the expressions of Bax and Bcl-2 were detected by SP immunohistochemistry method. Results Compared with model group, the number of apoptotic cells of the rats in nimodipine group was significantly decreased(P<0.05),the expression of Bax was significantly decreased (P<0.05),and the Bcl-2 expression was increased significantly(P<0.05).The morphological examination showed that the neurons of the rats in model group had serious necrosis and edema while the number of dead cells in nimodipine treatment group was reduced and the edema was improved.Conclusion Nimodipine has a protective effect on brain tissue of the rats with focal cerebral ischemia-reperfusion inj ury, which is closely related to the down-regulation of Bax and up-regulation of Bcl-2 and inhibition of the apoptosis of neuron.