雷公藤内酯醇对AD模型大鼠海马神经细胞凋亡的影响  

Effects of triptolide on neuronal apoptosis of hippocampus in AD model rats

作　　者：黄涛波[1] 吕诚[1] 胡小令[1] 桂婷[1] 

机构地区：[1]南昌大学医学院解剖学教研室,江西南昌330006

出　　处：《中国老年学杂志》2010年第19期2766-2770,共5页Chinese Journal of Gerontology

基　　金：国家自然科学基金(30660073)

摘　　要：目的探讨雷公藤内酯醇(TP)对阿尔茨海默病(AD)模型大鼠海马神经细胞凋亡及其相关蛋白表达的影响。方法健康雄性SD大鼠随机分为对照组、模型组及用药组。模型组给予双侧海马各一次性注射凝聚态Aβ1-40,Morris水迷宫实验判断模型成功与否。对照组大鼠双侧海马注射等量生理盐水。用药组大鼠在模型制作成功后每日腹腔注射TP0.4mg/kg,共15d。应用流式细胞仪、TUNEL染色、透射电镜技术检测各组大鼠海马神经细胞凋亡的变化,免疫组织化学法检测各组大鼠海马神经细胞细胞色素C和Bcl-2蛋白表达的变化。结果用药组大鼠海马神经细胞凋亡率较模型组明显降低(P<0.01),TUNEL染色阳性细胞数较模型组明显减少(P<0.01);用药组大鼠海马细胞色素C阳性产物数和平均光密度均较模型组明显减少(P<0.01),Bcl-2阳性细胞数和平均光密度均较模型组明显增加(P<0.01)。结论 TP对AD模型大鼠海马神经细胞凋亡有抑制作用,其机制可能与TP增加AD模型大鼠海马神经细胞Bcl-2蛋白表达、减少细胞色素C的释放有关。Objective To explore the effect of triptolide（TP） on the neuronal apoptosis and the expression of apoptosis-related proteins in hippocampus of AD model rats. Methods Healthy male SD rats were randomly divided into control,AD model and TP-treated groups. The AD model group was made by bilateral microinjection of Aβ1-40 into hippocampus in rats and Morris water maze test was used to judge the models success or not. The control group was made by bilateral microinjection of normal saline into hippocampus in rats.The TP-treated group rats were administered TP （0.4 mg·kg-1·d-1） intraperitoneally after the AD model was made successfully. 15 days later,the changes of neuronal apoptosis in hippocampus of each group were observed with flow cytometry and TUNEL staining and transmission electron microscopy,and the changes of cytochrome C and Bcl-2 protein expression in hippocampus of each group were observed by immunohistochemical staining. Results Compared with those of the AD model group,the apoptosis rate of neurons and the cell number of TUNEL positive staining in hippocampus of the TP-treated group were significantly decreased（P0.01）. The number and average optical density of cytochrome c positive products in hippocampus of the TP-treated group were obviously lower than those of the AD model group （P0.01）,and the cell number and average optical density of Bcl-2 positive staining were obviously higher than those of the AD model group （P0.01）. Conclusions TP can inhibit the neuronal apoptosis in hippocampus of the AD model group.Its mechanism may concern increasing the Bcl-2 expression and reducing the release of cytochrome c in hippocampus of the AD model group.

关 键 词：雷公藤内酯醇 Β-淀粉样蛋白 神经细胞凋亡 阿尔茨海默病 

分 类 号：R749.16[医药卫生—神经病学与精神病学]