白藜芦醇减轻慢性神经炎症所致的大鼠空间学习记忆减退  

Resveratrol attenuates spatial learning and memory deficits induced by chronic neuro-inflammation in rats

作　　者：龚其海[1] 杨丹莉[1] 石京山[1] 金凤[1] 

机构地区：[1]遵义医学院药理学教研室暨贵州省基础药理重点实验室,遵义563000

出　　处：《中国新药杂志》2011年第18期1817-1821,共5页Chinese Journal of New Drugs

基　　金：贵州省教育厅自然科学基金资助(黔科教(2009)0111)

摘　　要：目的:考察白藜芦醇对慢性炎症所致大鼠空间学习记忆减退的保护作用,探讨其作用机制。方法:雄性SD大鼠ip给予脂多糖20 mg·kg-1,每周1次,连续4周制备大鼠慢性神经炎症模型,同时ig给予白藜芦醇10,20,40 mg·kg-1·d-1,阳性组ig给予布洛芬40 mg·kg-1,连续26 d。给药d22行Morris水迷宫测定大鼠的空间学习记忆能力,连续5 d。实时定量PCR法测定大鼠海马组织肿瘤坏死因子α(TNF-α)、白细胞介素-1β(IL-1β)、诱导型一氧化氮合酶(iNOS)及环氧合酶-2(COX-2)mRNA的表达。结果:连续4周注射脂多糖(LPS)后,大鼠在定向航行实验中的逃避潜伏期明显增加,空间探索实验中的校正逃避潜伏期明显缩短,且海马组织中TNF-α,IL-1β,NOS2及COX-2基因的mRNA表达水平增加;白藜芦醇和布洛芬组大鼠定向航行实验中的逃避潜伏期明显缩短,空间探索实验中的校正逃避潜伏期延长,海马组织中TNF-α,IL-1β,NOS2及COX-2基因的mRNA表达水平降低。结论:白藜芦醇可减轻慢性神经炎症诱导的大鼠记忆能力减退,其机制可能与降低海马组织中TNF-α,IL-1β,NOS2及COX-2基因的mRNA表达水平有关。Objective： To investigate the protective effect of resveratrol on spatial learning and memory def icits induced by chronic neuro-inflammation in rats, and explore the possible mechanisms. Methods： Chronic neuro-inflammation was induced by lipopolysaccharide （LPS, 20 mg·kg^-1, ip, once per week for 4 weeks） in male Sprague-Dawley rats. Rats were administrated with oral resveratrol at doses of 10, 20 and 40 mg. kg^-1, once daily for 26 days, and with oral ibuprofen （Ibu） at 40 mg·kg^-1 as positive control. After treatment with Ibu or resveratrol for 22 d, the ability of spatial learning and memory of rats was tested by Morris water maze, and the mRNA expressions of TNF-α,IL-1β, NOS2 and COX-2 in hippocampus were detected by real time PCR. Results： LPS injection for consecutive 4 weeks increased escape latency in the place navigation test, and decreased adjusted escape latency in spatial probe test. Meanwhile, LPS injection increased the mRNA expressions of TNF-α,IL-1β, NOS2 and COX-2 in hippocampus. Resveratrol or Ibu significantly shortened escape latency in the place navigation test, and increased adjusted escape latency in spatial probe test. Furthermore, resveratrol or Ibu significantly decreased the mRNA expressions of TNF-α,IL-1β, NOS2 and COX-2 in rat hippocampus. Conclusion： Resveratrol can attenuate spatial learning and memory deficits induced by chronic neuro-inflammation in rats, which may be partly due to the inhibition of expressions of TNF-α,IL-1β, NOS2 and COX-2 mRNA in hippoeampus.

关 键 词：白藜芦醇 脂多糖 炎症 学习 记忆 大鼠 

分 类 号：R964[医药卫生—药理学]