靶蛋白信号通路相关蛋白在血管性痴呆大鼠海马CA1区的表达

Expression of PI3K/Akt/mTOR signaling pathway-related proteins in hippocampal CA1 area of vascular dementia rats

目的观察磷脂酰肌醇3激酶(phosphatidylinositol 3-kinase,PI3K)/蛋白激酶B(protein kinase B,Akt)/哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)信号通路相关蛋白Akt和mTOR在血管性痴呆大鼠海马CA1区的表达及变化情况。方法选择SD大鼠72只,随机分为假手术组、血管性痴呆模型组(模型组)和PI3K抑制剂LY294002组(LY294002组),每组24只。每组又随机分为模型制备成功后1、2、4、8周4个时间点,每个时间点6只。采用改良Pulsinelli四血管阻断法制备血管性痴呆大鼠模型。免疫组织化学法检测Akt、mTOR蛋白的表达情况。结果假手术组海马CA1区不同时间点可见少量Akt和mTOR蛋白阳性表达。与假手术组比较,模型组和LY294002组1、2、4、8周Akt、mTOR蛋白表达明显增高;与模型组比较,LY294002组1、2、4、8周Akt[(8.83±1.47)个/高倍视野vs(12.50±1.87)个/高倍视野,(12.83±2.32)个/高倍视野vs(20.67±4.23)个/高倍视野,(29.00±2.60)个/高倍视野vs(40.33±3.33)个/高倍视野,(24.33±4.32)个/高倍视野vs(35.00±4.15)个/高倍视野]、mTOR蛋白表达明显降低,差异有统计学意义(P<0.05,P<0.01)。结论 Akt和mTOR蛋白在血管性痴呆大鼠海马CA1区过度表达,可能是血管性痴呆发生、发展的重要机制之一。

Objective To study the expression of PI3K/Akt/mTOR signaling pathway-related pro teins （Aktand mTOR） in hippoeampal CA1 area of vascular dementia rats. Methods Seventy-two SD rats were randomly divided into sham operatiion group, vascular dementia model group and PI3K inhibitor LY294002 group （24 in each group）. The animals in each group were further divid- ed into 1-week, 2-week, 4-week and 8-week groups after the model was established （6 in each group）. A rat vascular dementia model was established using the modified Pulsinelli 4-vessel bloc- king method. Expressions of Akt and roTOR proteins were detected with immunohistochemial staining. Results A small number of Akt and mTOR proteins were expressed in hippocampal CA1 area of sham operation group at different time points. The expression levels of Akt and mTOR proteins were significantly higher in model group and PI3K inhibitor LY294002 group than in model group and were significantly lower in PI3K inhibitor LY294002 group than in sham operation group at different time points （P〈0.05,P〈0.01）. Conclusion Overexpression of Akt and mTOR proteins in hippocampal CA1 area of vascular dementia rats is one of the important mechanisms underlying the occurrence and progression of vascular dementia.