【摘要】 目的观察App17肽对脑室注射链脲佐菌素的大鼠海马神经元凋亡相关蛋白表达的影响,探讨胰岛素信号转导通路障碍对神经元存活的作用。方法脑室注射链脲佐菌素(STZ)制作大鼠痴呆模型。3周后,皮下注射App17肽。4周后取脑组织做Bcl-2、Bax、CytoC免疫组织化学染色及Western blotting半定量分析。结果模型组大鼠海马内Bax、CytoC阳性反应神经元细胞数目多,胞质深染,细胞计数与正常组及治疗组有显著性差异(P<0.01);模型组大鼠海马内Bcl-2阳性细胞数目少,胞质染色淡,细胞计数与正常组及治疗组有显著性差异(P<0.01)。Western blotting半定量分析可见、Bcl-2、Bax、CytoC出现清晰的条带,组间可见较明显的差异(P<0.01)。结论脑室注射STZ的大鼠海马内促进凋亡的Bax、CytoC表达增加;抑制凋亡的Bcl-2表达降低。App17肽可影响上述蛋白的表达,使之接近正常。胰岛素信号转导通路对神经元存活有一定作用。更多还原

【Abstract】 Objective To investigate the effect of insulin signaling pathway on neuronal survival and the effect of the peptide App17 on regulating the expression of some apoptosis-related proteins in neurons of the hippocampus through intracerebrorentricular injection of streptozotocin in rats. Methods The rats were injected with App17 peptide subcutaneously three weeks after the model group was established by intracerebrorentricular injection of streptozotocin.After the four-week treament,the expressions of the apoptosis-related proteins,such as Bcl-2,Bax,CytoC in neurons of the hippocampus were tested with immunohistochemical staining and Western blotting.Results Bax,CytoC positive neurons were widely distributed in the hippocampus of the model group,and the cytoplasm was darkly stained.In contrast,the positive neurons for Bax,CytoC in hippocampus were poorly stained in the control group and the treated group,and appeared significant difference in cell counting as compared with model group.Bcl-2 positive neurons were widely distributed in the hippocampus in the control group and the treated group,and the cytoplasm was darkly stained while its positive neurons were poorly stained in the model group,and appeared significant difference in cell counting as compared with the model group.From the Western blotting clear bars could be seen in the three groups and there was a significant difference between them.Conclusions The expression of Bax,CytoC increased in the hippocampus in the rats with intracerebrorentricular injection of streptozotocin while the expression of Bcl-2 decreased.The App17 peptide could promote the rehabilitation of the abnormal expression of the three proteins to some extent.The insulin signaling pathway could affect the survival of the neurons in rats’ hippocampus.更多还原