二苯乙烯苷对APP/PS1小鼠老年斑形成和炎症反应的影响

Effects of 2,3,5,4'-tetrahydroxy-stilbene-2-O-β-D-glycoside on Senile Plaques Formation and Inflammatory Response in APP/PS1 Mice

目的观察二苯乙烯苷(TSG)对APP/PS1双转基因小鼠脑内皮层及海马老年斑和β淀粉样蛋白(Aβ)的形成,以及小胶质细胞和星形胶质细胞活化的影响。方法 64只5月龄APP/PS1小鼠,随机分为模型组(n=16)、多奈哌齐组(n=16)、TSG低剂量(0.05 g/kg)组(n=16)和TSG高剂量(0.1 g/kg)组(n=16);32只同月龄野生型(WT)小鼠随机分为正常对照组(n=16)和TSG高剂量(0.1 g/kg)WT组(n=16)。正常对照组与模型组予蒸馏水灌胃,其余各组分别予相应药物灌胃。给药7个月(12月龄)后,应用新物体识别实验检测各组学习记忆功能,刚果红染色法检测脑部淀粉样斑块沉积情况,免疫组化法观察脑部Aβ_(40/42)沉积以及离子钙结合蛋白(Iba1)和胶质纤维酸性蛋白(GFAP)表达。结果与模型组相比,各治疗组小鼠新物体识别指数明显增加(P<0.01),脑部斑块沉积减少(P<0.05),Aβ_(40/42)沉积下降(P<0.05),Iba1和GFAP表达降低(P<0.05)。结论 TSG能改善APP/PS1小鼠的学习记忆,减少Aβ的沉积和老年斑形成,降低炎症反应,小剂量即可发挥作用,作用与多奈哌齐类似。

Objective To observe the effects of 2,3,5,4'-tetrahydroxy-stilbene-2-O-β-D-glycoside(TSG) on formation of senile plaques and beta amyloid(Aβ), as well as activation of microglia and astrocytes, in cortex and hippocampus of APP/PS1 double transgenic mice.Methods A total of 64 five-month-old APP/PS1 mice were randomly divided into model group(n=16), low-dose TSG(0.05 g/kg) group(n=16), high-dose TSG(0.1 g/kg) group(n=16), and donepezil group(n=16); other 32 same age wild type(WT) mice were randomly divided into normal control group(n=16) and high-dose TSG(0.1 g/kg)WT group(n=16). The normal control group and model group were given distilled water, and the other groups were given the corresponding drugs intragastrically. The mice were tested with object recognition test, the deposition of plaques in brain was detected with Congo red staining, and the expression of Aβ40/42, ionized calcium binding adapter molecule 1(Iba1) and glial fibrillary acidic protein(GFAP) with immunohistochemistry after sevenmonths of treatment(twelve-month-old).Results Compared with the model group, the discrimination index significantly increased(P<0.01), the deposition of plaques decreased in brain(P<0.05), and the expression of Aβ40/42, Iba1 and GFAP all significantly decreased in each treatment group(P<0.05).Conclusion TSG can improve learning and memory of APP/PS1 transgenic mice, reduce Aβ deposition and senile plaques, and reduce the inflammatory response, even in low-dose, which is similar to that of donepezil.