参麻益智汤对拟阿尔海默病模型小鼠的治疗作用及其机制研究

摘要

目的:研究参麻益智汤(SYD)对拟阿尔茨海默病(AD)模型小鼠的治疗作用及其机制.方法:选用昆明种小鼠,腹腔注射D-半乳糖和灌胃三氯化铝(AlCl3)90 d制备AD小鼠模型,3个治疗组在造模的后40 d分别灌胃低、中、高剂量SYD.从第86 d起灌胃结束后进行Morris水迷宫测试,连续5 d.水迷宫测试结束后检测小鼠海马组织超氧化物歧化酶(SOD)的活性和丙二醛(MDA)的含量,用荧光实时定量PCR的方法观察小鼠海马bax mRNA和bcl-2 mRNA的表达,用免疫组化方法观察小鼠海马caspase-3蛋白的表达.结果:与AD模型组比较,SYD中剂量组小鼠水迷宫学习成绩较好(P<0.05);SYD中、高剂量组小鼠海马组织内SOD活性增高,MDA含量降低(P<0.05);中剂量的SYD能下调小鼠海马bax mRNA的表达和caspase-3蛋白的表达(P<0.01),各剂量的SYD对bcl-2 mRNA的表达均未见明显影响(P>0.05).结论:SYD可以改善拟AD小鼠学习记忆能力,其机制可能与SYD提高小鼠海马神经元的抗氧化能力(SOD活性升高,MDA含量降低)、下调bax mRNA和caspase-3蛋白的表达、进而减少小鼠海马神经元的凋亡有关.%AIM : To study the therapeutic effect and possihle mechanisms of Shenma Yizhi decoction ( SYD ) on the mouse model of Alzheimer disease ( AD ).METHODS: The Kunming mice were treated with D - galactose and AIC13 for 90 d to establish the AD animal model.The AD model mice in therapy groups were treated with different doses of SYD for 40 days ( beginning at the 51th day of AlCl3 exposure ).Morris water maze test was used to assess the behavior performance of the mice with different treatment.The activity of superoxide dismutase( SOD ) and the content of malondialdehyde( MDA ) in hippocampus were measured and the mRNA expression of bax and bcl - 2 was quantified by real - time PCR.The protein level of caspase - 3 in hippocampus was also determined by immunohistochemistry after the treatments.RESULTS : Compared to AD model group, the mice in medium - dose SYD group showed better performance in Morris water maze test ( P ＜ 0.05 ).SYD at medium and high doses markedly increased the activity of SOD and decreased the elevation of MDA level ( P ＜0.05 ).SYD at medium dose significantly down - regulated the mRNA expression of bax and the protein level of caspase -3 in hippocampus ( P ＜0.01 ).No significant influence of SYD at different doses on the mRNA expression of bcl - 2 was observed ( P ＞ 0.05 ).CONCLUSION: SYD at medium dose prevents neurons from apoptosis and improves the ability of learning and memory in AD model mice by enhancing the capacity of anti - oxidation and down - regulating the expression of bax mRNA and caspase - 3 protein in hippocampus.