白藜芦醇改善脂多糖诱导的大鼠学习记忆减退与抑制炎症相关蛋白表达有关  

Resveratrol improves lipopolysaccharide-induced learning and memory impairment through inhibition of inflammation-related protein expression in rats

作　　者：李明刚 邓媛媛 龚其海 

机构地区：[1]遵义医学院基础药理教育部重点实验室暨特色民族药教育部国际合作联合实验室,贵州遵义563099 [2]遵义市播州区人民医院,贵州遵义563100

出　　处：《遵义医学院学报》2017年第5期491-495,共5页Journal of Zunyi Medical University

基　　金：教育部"长江学者和创新团队发展计划"创新团队(NO:IRT_17R113)

摘　　要：目的观察白藜芦醇对阿尔茨海默病(AD)样神经炎症大鼠模型的作用及其机制。方法雄性SD大鼠随机分空白对照组(n=10),模型组(n=15),阳性药组(n=15),白藜芦醇10、20、40 mg/kg剂量组(n=15)。除空白对照组外,各组大鼠腹腔注射脂多糖(0.5 mg/kg),空白对照组注射相同体积的溶媒,每周1次,共13周。造模期间,阳性药组灌胃布洛芬40mg/kg,白藜芦醇不同剂量组分别每日一次灌胃白藜芦醇10、20、40 mg/kg,连续13周,空白对照组和模型组以等体积蒸馏水灌胃。Morris水迷宫检测大鼠的空间学习和记忆能力;透射电镜观察大鼠海马神经元超微结构;免疫印迹法检测肿瘤坏死因子-α(TNF-α)、环氧合酶2(COX-2)和白细胞介素-1β(IL-1β)的蛋白表达。结果白藜芦醇和布洛芬显著缩短模型大鼠的空间逃避潜伏期;减轻海马神经元超微结构损伤;降低海马组织TNF-α、COX-2和IL-1β的过度表达。结论白藜芦醇通过下调炎症相关蛋白的表达,改善LPS诱导的大鼠学习记忆减退。Objective To observe the effects of resveratrol （Res） on Alzheimerg disease （AD） -like neuroin- flammation in rats and explore its mechanisms. Methods Male SD rats were randomly divided into sham - operated group （n = 10） as control group, model group （n = 15 ）, positive group and model ＋ Resveratrol （Res 10,20 and 40 mg/kg） groups （n = 15 per groups）. To construct inflammatory model,rats in the model group were intraperitoneally injected with lipopolysaccharide （LPS） at the dose of 0.5 mg/kg once a week continuously for 13 weeks. Meanwhile, the intragastric administration of distilled water, Ibuprofen （ IBU,40 mg/kg） or Res （ 10,20 and 40 mg/kg） once a day for each group. Morris water maze was applied to investigate the cognitive function. E- lectron microscope was used to detect the hippocampal neuronal morphology. The expression of tumor necrosis factor （ TNF - α）, interleukin - 10 （ IL - 10 ） and cyclooxygenase - 2 （ COX - 2 ） was analyzed by western blot assay. Results The swimming distances in model group were obviously longer than those in sham group, while Res or IBU treatment significantly shortened the swimming distances compared with those in model rats. Electron mi- croscopy showed that Res significantly reduced the ultrastructural damage of hippocampal neurons. Moreover, the overexpression of TNF - cx, COX - 2 and IL - 1 {3 protein in the hippocampus were significantly decreased after Res treatment. Conclusion Res improves spatial learning and memory in LPS - induced rats, and the possible mechanisms are due to inhibiting the expressions of pro - inflammatory cytokines.

关 键 词：白藜芦醇 脂多糖 阿尔茨海默病 炎症 大鼠 

分 类 号：R965[医药卫生—药理学]