胰岛素信号通路PI3K／Akt对海马神经元β-淀粉样前体蛋白裂解酶1mRNA水平的影晌

目的通过胰岛素和磷脂酰肌醇-3激酶（P13K）抑制剂渥曼青霉素（wortmannin）对P13K／丝氨酸苏氨酸蛋白激酶（P13K／Akt）信号通路的激活和抑制作用，观察P13K／Akt信号通路对海马神经元β-淀粉样前体蛋白裂解酶1（BACEl）mRNA水平表达的影响。方法20只sD大鼠随机分为空白对照组、假手术组、胰岛素组和渥曼青霉素组，海马立体定向注射胰岛素和P13K抑制剂渥曼青霉素。逆转录一聚合酶链反应（RT-PCR）检测P13K／Akt信号传导下游蛋白Akt以及BACEImRNA水平。结果注射胰岛素的海马P13K信号通路下游信号分子：AktmRNA表达上调（分别较空白和阴性对照组P=0．047，P=0．002），而BACElmRNA表达下调（分别较空白和阴性对照组P=0．004，P=0．01）。渥曼青霉素组的P13K下游信号分子AktmRNA表达明显被抑制（分别较空白和阴性对照组P=0．002，P=0．039），同时BACEImRNA的表达较对照组上调（分别较空白和阴性对照组P=0．039，P=0．018）。结论胰岛素信号通路P13K／AM可以调节BACEl的转录水平参与阿尔茨海默病的发病机制。

PI3K / Akt Signaling Pathway on Expression of BACE! mRNA in Hippocampus Neurons

Objective To investigate the effect of beta-site amyloid precursor protein cleaving enzyme-1 （BACE1） mRNA on phosphatidylinositol-3 kinase / serine threonine kinase（ PI3K / Akt） signaling pathway in the hippocampus neurons of rat brain. Methods Insulin and the specific inhibitor of PI3K Wortmannin were used to activate and inhibit the signaling pathway ,20SD rats randomly divided into four group ：blank control group, sham-operated group, insulin group and Wortmannin group. RT-PCR were used to analyse the proteins related to the insulin sig- naling Akt and BACE1 mRNA. Results The expression of signaling pathway downstream molecules Akt mRNA were up-regulated（p = 0. 047, p = 0. 002） ,the expression of BACE1 mRNA significantly down-regulated （p = 0. 004 ,p = 0. 01 ）in insulin group. The expression of BACE1 mRNA was opposite after treatment with inhibitor of PI3K（ p =0. 039 ,p =0. 01g） ,Akt mRNA were also inhibited（p =0. 002 ,p =0. 039 ）. Conclusion PI3K / Akt signaling pathway might effect the expression of BACE1 ,which demonstrates that impaired signaling pathway shoud make the amyloid precursor protein easy to be processed by BACE1 ,thus to involve the pathology of Alzheimer＇s disease.