APP17肽对2型糖尿病KK小鼠海马神经元超微结构和InsR、IRS-1的影响

为观察APP1 7肽对糖尿病KKAy小鼠 (以下简称KK小鼠 )脑海马神经元部分信号转导蛋白表达的影响 ,并探讨APP1 7肽对神经元的营养作用 ,将KK小鼠分为正常对照组 (C组 )、糖尿病组 (DM组 )和APP1 7肽治疗组(DM +APP1 7P组 ,给予APP1 7肽皮下注射 )。 1 2周后将 3组小鼠处死 ,心脏取血测血糖和血浆胰岛素 ;灌注固定后 ,取海马送电镜检查并作免疫组织化学染色。结果显示 :①DM组与DM +APP1 7P组的血糖、胰岛素水平比C组显著升高 (P <0 .0 5 ) ,但是DM组与DM +APP1 7P组之间无显著差异 ;②DM组海马神经元胰岛素受体 (InsR)、胰岛素受体底物 1 (IRS 1 )的表达低于C组和DM +APP1 7P组 (P <0 .0 5 ) ;③海马超微结构显示DM组海马神经元线粒体肿胀 ,未见凋亡的神经元 ,DM +APP1 7P组和C组神经元基本正常。提示 :APP1 7肽作为神经营养因子能激活信息转导通路 ,从而对神经元凋亡有改善作用。

Effect of APP17 Peptide on the Hippocampal Neurons Ultrastructure and Expression of InsR, Ins-1 in Type 2 Diabetic KKAy Mice

The objective of the study was to investigate the expression of apoptotic-related proteins in hippocampal neurons of KK mice and the hippocampus ultrastructure in diabetic KK mice. KK mice were divided into three groups: normal control group, diabetic group and diabetic group treated with APP17-mer peptide. After 12 weeks, crystat sections of mouse brain were prepared and immunohistochemically stained for InsR, IRS-1. Three groups of the mice were observed and analyzed by electron microscopy. The levels of blood glucose and plasma insulin in DM group and DM APP17P group were significantly increased and compared with C group. There were no significant difference between DM group and DM APP17P group. The expression of InsR, IRS-1 significantly decreased in diabetic mice as compared with normal controls (P<0.05), and find mitochondria edema in hippocampus in DM group. APP17 peptide may activate the signal transductive pathway. It may also improve the apoptosis of neuron in type 2 diabetic KK mice.