二苯乙烯苷对APP/PS1双转基因阿尔茨海默病小鼠脑内β淀粉样前体蛋白及分拣蛋白相关受体1 mRNA表达的影响

Effect of TSG on protein expression of APP in APP / PS1 double transgenic AD mice brain tissues

目的研究二苯乙烯苷(TSG)对APP/PS1双转基因小鼠脑内β淀粉样前体蛋白(APP)及分拣蛋白相关受体(SORL)1表达的影响。方法 3月龄APP/PS1双转基因鼠50只,随机分为模型组、阳性药石杉碱甲组、TSG高、中及低(0.3,0.1,0.033 g/kg)剂量组,另取同龄C5B7L/6J鼠10只为正常对照组。各组给予相应药物60 d后,采用苏木素-伊红(HE)染色法观察小鼠海马神经元的一般结构;免疫组化SABC法检测各组小鼠脑组织APP蛋白的表达。FQ-PCR法检测SORL1 mRNA表达情况。结果与模型组比较,各组小鼠大脑皮层及海马区形态均有不同程度恢复;APP表达量均下降(P<0.01,P<0.05);SORL1 mRNA表达均有所上调(P<0.05)。结论 TSG治疗阿尔茨海默病(AD)的机制可能与促进SORL1 mRNA生成、抑制APP异常代谢、减少老年斑的生成等机制有关。

Objective To observe the effect of TSG on gene expression of β-amyloid precursor protein（APP） and sortilin-related receptor 1 （ SORL1 ） in APP/PS1 double transgenic mice brain tissues. Methods Fifty three-months-old APP/PS1 double transgenic mice were randomly divided into model,huperzine A,high-,mid- and low-dose groups of TSG（0.3,0.1,0.033 g/kg） ,with 10 mice in each group,and another 10 same age CSBTL/6J mice as normal control group. After medication corresponding drugs for 60 days, HE staining was used to ob- serve the general structure of hippocampal neurons, the expression of APP in brain tissue was assayed by immunohistochemical SABC method, and FQ-PCR method was used to detect the expression of SORL1 mRNA. Results Compared with those of model group,the cerebral cortex and hippocampus in each group were recovered in different degree, the protein expression of APP was down-regulated（ P〈0.01, P〈0.05 ）, the expression of SORL1 mRNA was up-regulated （P〈0.05）. Conclusions TSG has a certain preventive and therapeutic effect on AD that might be related to promoting the generation of SORL1 mRNA, inhibition of the protein expression of APP and reducing the formation of senile plaques.