二苯乙烯苷对APP/PS1双转基因小鼠海马区病理形态学及脑BACE 1表达的影响

摘要

目的：观察二苯乙烯苷(TSG)对 APP/PS1双转基因小鼠海马区病理形态学变化和脑组织中β-淀粉样前体蛋白裂解酶-1(BACE1)表达的影响，探讨其作用的可能机制，为临床应用提供实验依据。方法50只3月龄 APP/PS1双转基因小鼠，随机分为TSG低剂量(0.033 g·kg-1·d-1)组、TSG中剂量(0.1 g·kg-1·d-1)组、TSG高剂量(0.3 g·kg-1·d-1)组、石杉碱甲(阳性对照)组及模型组，正常对照组为10只同龄 C5B7L/6J 小鼠。各组给予60 d 相应药物后，苏木精-伊红(HE)染色法观察海马区病理形态学变化；用 Western blotting 法检测小鼠脑组织 BACE1蛋白表达水平。结果与模型组相比，各治疗组小鼠海马区形态均有不同程度的改善；BACE1表达水平均显著降低(P <0.01)。TSG各剂量组BACE1的表达量与石杉碱甲组相比，差异无统计学意义(P >0.05)。结论 TSG治疗阿尔茨海默病的机制可能与降低BACE1表达水平，减少β淀粉样蛋白(Aβ)产生，改善神经元损伤等有关。%Objective To observe the effects of 2,3,5,4'tetrahydroxy-stilbene-2-O-β-D-glycoside (TSG) on the pathomorphological changes of hippocampus and on the expressions ofβ-amyloid precursor protein cleav-age enzyme1 (BACE1)in APP/PS1 double transgenic mice,so as to study its possible mechanisms and to pro-vide experimental evidences for treating AD by TSG. Methods Fifty three-month-old APP/PS1 double transgenic mice were randomly divided into a low-dose TSG (0.033 g·kg-1 ·d-1 )group,a mid-dose TSG (0.1 g·kg-1 ·d-1 )group,a high-dose TSG (0.3 g·kg-1 ·d-1 )group,a huperzine A (positive control)group and an APP/PS1 model group.The normal control group had 10 C5B7L/6J mice with the same age as APP/PS1 doub-le transgenic mice.HE staining was used to observe the pathomorphological changes of hippocampus and the expressions of BACE1 protein in mice brain tissues were assayed by using Western blotting after all mice were given corresponding medicine for sixty days. Results By comparing with model group,the hippocampal con-figurations in every treated group were recovered at different degree,the expressions of BACE1 were markedly down-regulated (P<0.01).Compared with huperzine A group,the level of BACE1 expression had no signifi-cant difference (P>0.05). Conclusion The mechanism of TSG in treatment of AD might be related with down-regulating the expressions of BACE1 ,decreasing the genesis ofβ-amyloid protein and relieving the neu-rons damages.