白藜芦醇对阿尔茨海默病大鼠海马组织中小胶质细胞及白细胞介素-1β表达抑制作用的实验研究

The inhibiting effect of resveratrol on microglial and IL-1β expression in the hippocampal of rats with Alzheimer′s disease

目的探讨白藜芦醇(resveratrol,Res)对阿尔茨海默病(Alzheimer′s disease,AD)大鼠海马组织中小胶质细胞的增殖活化以及白细胞介素-1β(IL-1β)表达的影响。方法采用去卵巢合并D-半乳糖(100mg/kg)注射制备AD大鼠模型,60只雌性Wistar大鼠随机分为模型组、Res低、中、高剂量组(20、40、80mg/kg)、戊酸雌二醇组(0.8mg/kg)及假手术组(蒸馏水),连续灌胃12周,采用在体心脏灌流法,固定大鼠海马脑组织,利用免疫组化法分别检测大鼠海马组织小胶质细胞离子钙接头蛋白(Iba-1)以及IL-1β的表达。采用SPSS 16.0软件进行统计分析,免疫组化结果采用单因素方差分析,检验水准α=0.05。结果经单因素方差分析,6个组Iba-1的表达量总体均数差异有统计学意义[F(5,66)=30.632,P<0.01]。多重比较结果显示:模型组Iba-1表达量明显高于假手术组(P<0.05);Res低剂量组Iba-1表达量低于模型组(P<0.05);Res中、高剂量组以及戊酸雌二醇组Iba-1表达量低于模型组(P<0.01);Res中剂量组Iba-1表达量低于戊酸雌二醇组(P<0.01)。6个组IL-1β的表达量总体均数差异有统计学意义[F(5,66)=11.553,P<0.01]。多重比较结果显示:模型组IL-1β表达量高于假手术组(P<0.01);Res低、中、高剂量组以及戊酸雌二醇组IL-1β表达量低于模型组(P<0.01)。结论 Res可以抑制AD大鼠海马中过度增殖活化的小胶质细胞并且减少脑组织中IL-1β的表达,从而对AD大鼠神经系统起到保护作用。

Objective To assess the inhibiting effect of resveratrol（Res）on the proliferation and activation of microglial and IL-1βexpression in hippocampus of AD rats. Methods Sixty AD rats were randomly divided into six groups including sham control group,model group,estradiol valerate group and Res 20,40,80mg/kg group.At the end of 12 weeks,the heart perfusion in vivo was done and then the hippocampus was fixed.Subsequently,the changes of hippocampal microglial and IL-1βexpression were tested by immunohistochemistry. Results According to the result of one-way analysis of variance,the expression levels of Iba-1[F（5,66）=30.632,P〈0.01]and IL-1β[F（5,66）=11.553,P〈0.01]in rats in six groups were significantly different.Multiple comparisons showed that the expression of Iba-1in rats in sham group was significantly lower compared with that in model group（P〈0.05）.Moreover,compared to rats in model group,the levels of Iba-1and IL-1βin rats received 20,40 and 80 mg/kg Res as well as received estradiol valerate were significantly lower（P〈0.01）.While,it was lower in rats received 40mg/kg of Ras compared with estradiol valerate（P〈0.01）. Conclusions Res can inhibit the proliferation and activation of microglial and IL-1βexpression in hippocampus of AD rats.