桂枝加葛根汤对神经炎症小鼠海马空间记忆、细胞因子和小胶质细胞的影响  

Effects of Guizhi Plus Gegen Decoction on Spacial Memory and Cytokines and Microglia in Hippocampus of Neuroinflammatory Mice

作　　者：徐颖[1] 张利青[1] 夏趁意[1] 董献文[1] 赵妍[1] 王星禹[1] 

机构地区：[1]上海中医药大学生理教研室,上海201203

出　　处：《中国实验方剂学杂志》2013年第14期186-190,共5页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(81274119);上海市教育委员会科研创新项目(13YZ050);上海市教育委员会预算内科研项目(2010JW04);上海市教育委员会重点学科项目(J50301)

摘　　要：目的:探讨桂枝加葛根汤对脂多糖(LPS)诱导神经炎症小鼠海马空间记忆、炎性细胞因子和小胶质细胞激活的影响及可能的作用机制。方法:将63只雄性ICR小鼠随机分为5组:正常对照组(Control,n=13)、神经炎症模型组(Model,n=13)、桂枝加葛根汤低剂量组(GGD-low,n=10)、桂枝加葛根汤高剂量组(GGD-high,n=14)、二甲基四环素阳性对照组(Positive control,n=13,0.05 g.kg-1,每日1次,连续3 d)。给予小鼠ip LPS(0.33 mg.kg-1)建立AD的神经炎症模型,桂枝加葛根汤低、高剂量(6,12 g.kg-1)治疗4周后分别采用Morris水迷宫、ELISA和免疫荧光法检测观察桂枝加葛根汤对神经炎症小鼠空间记忆、海马细胞因子肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)含量以及小胶质细胞的激活现象的影响。结果:Morris水迷宫结果显示,LPS诱导后小鼠的逃避潜伏期明显比正常对照组延长(P<0.05),桂枝加葛根汤低、高剂量治疗后小鼠逃避潜伏期均明显比模型组缩短(P<0.05,P<0.01);LPS导致小鼠海马TNF-α,IL-1β含量显著增高(P<0.01),小胶质细胞则表现为数量增多且呈放射状等激活现象,桂枝加葛根汤治疗后TNF-α,IL-1β含量则不同程度地明显降低(P<0.05),小胶质细胞激活状态改善。结论:桂枝加葛根汤对LPS诱导的神经炎症小鼠海马空间记忆障碍具有改善作用,其机制可能与调节海马小胶质细胞激活和炎性细胞因子TNF-α和IL-1β含量的作用有关。Objective： The aim of this study was to explore the effects of Guizhi plus Gegen decoction（GGD） on spacial memory and inflammatory cytokines and microglia in hippocampus of neuroinflammatory mice induced by lipopolysaccharides（LPS） and its probable mechanism.Method： Totally 63 male ICR mice were randomly divided into 5 groups,i ethe normal control group（Control,n = 13）,the model group（Model,n = 13）,the low dose GGD group（GGD-low,n = 10）,the high dose GGD group（GGD-high,n = 14）,and the Minocycline positive control（Positive control,n = 13,0.05 g.kg-1）.AD neuroinflammatory model mice were established through intraperitoneally injected with LPS（0.33 mg.kg-1）.Mice had been administered by gastrogavage for 4 weeks with low dose GGD（6 g.kg-1） or high dose GGD（12 g.kg-1）.Then,Morris water maze were practiced respectively to observe the effects of GGD on spacial memory,and inflammatory cytokines and microglia of hippocampus in neuroinflammatory mice were tested by ELISA and immunofluoresent assay.Result： The escape latency of model mice induced by LPS increased significantly（P 0.05） in Morris water maze.After treated with low dose or high dose GGD,the model mice had evidently shortened their escape latency（P 0.05,P 0.01）.Also,LPS increased significantly content of tumor necrosis factor-α（TNF-α） and interleuktin-1β（IL-1β） in hippocampus（P 0.01）.Microglia in hippocampus of Model mice are characterized by the rise in the numbers and activated phenomenon such as radial.GGD reduced the content of TNF-α and IL-1β at some degree（P 0.05）,and regulated the activated phenomenon of microglia.Conclusion： These results indicate that GGD could improve spacial memory disorder in neuroinflammatory mice induced by LPS.Its mechanism may be possibly correlated with its regulatory effects of GGD on activated microglia and content of TNF-α and IL-1β in hippocampus.

关 键 词：神经炎症 空间记忆 炎性细胞因子 小胶质细胞 桂枝加葛根汤 

分 类 号：R285.1[医药卫生—中药学]