【摘要】 目的了解托吡酯(topiramate)对大鼠局灶性脑缺血再灌注后神经细胞凋亡和热休克蛋白-70(HSP-70)蛋白表达的影响,探讨托吡酯的神经保护作用机制。方法用线栓法制备SD大鼠大脑中动脉阻塞再灌注(MCAO)模型,托吡酯100mg/kg灌胃,qd×3,应用原位末端标记(TUNEL)和HSP-70免疫组化染色分别观察大鼠脑缺血再灌注后神经细胞凋亡和HSP-70表达。结果脑缺血再灌注后2h即出现凋亡细胞,并逐渐增加,2d达高峰,之后逐渐减少。托吡酯干预后,凋亡神经细胞减少,其中再灌注12～48h与对照组比较差异有显著性P<0·01。脑缺血再灌注后HSP-70的表达于2h逐渐增加,24h达高峰,72h后逐渐降低。托吡酯干预后,再灌注12h～72hHSP-70表达较对照组显著升高。结论HSP-70及神经细胞凋亡均参与了脑缺血的病理生理过程,托吡酯具有抑制细胞凋亡和神经保护作用。更多还原

【Abstract】 Objective To investigate the effects of topiramate on neuronal apoptosis and expression of heat-shock-proteins-70(HSP-70) after focal cerebral ischemia and reperfusion in rats,and to explore the neuroprotective mechanisms of topiramate.Methods A model of focal ischemic reperfusion in SD rats was induced by intraluminal middle cerebral artery occlusion(MCAO) with a nylon monofilament suture.Topiramate(100 mg/kg)orally everyday before reperfusion.Apoptosis was characterized by terminal deoxynucleotide transferase mediated uridine 5’-triphosphate-biotin nick end-labeling(TUNEL) staining.The expression of HSP-70 in the hippocampus was detected with immunohis-tochemical method.Results HSP-70 expression was detected in the cortex of ischemic hemisphere as early as two hours after reperfusion and peaked at 12 hours and one day in cortex,respectively.With topiramate intervened the HSP-70 expression increased.TUNEL-positive cells were observed two hours after reperfusion and peaked at two days after reperfusion in the cortex respectively.Conclusion HSP-70 and Apoptosis are involved in pathophysiologic process of cerebral ischemia.Topiramate can inhibit apoptosis and protect nerves.更多还原