雷公藤氯内酯醇对拟阿尔茨海默病样大鼠海马神经元的保护作用  

The protective effect of tripchlorolide on the hippocampal neurons of the Alzheimer′s disease rat model

作　　者：王元伟[1] 郑关毅[1] 

机构地区：[1]沭阳县人民医院神经内科,江苏沭阳223600

出　　处：《国际内科学杂志》2008年第10期564-566,581,F0003,共5页International Journal of Internal Medicine

摘　　要：目的研究雷公藤氯内酯醇(T4)对拟阿尔茨海默病(AD)样大鼠海马神经元的保护作用及可能机制。方法应用脑立体定向技术向SD大鼠海马背侧注射凝聚态β-淀粉样蛋白(Aβ)25-35建立具有拟AD样Aβ沉积病理变化的大鼠模型。35只大鼠随机分为正常对照组、假注射组、模型组、T4低剂量(5μg/kg)组、T4高剂量(20μg/kg)组,每组7只。于模型制作后7d收集脑组织标本,采用Western blot方法观察海马组织核因子(NF-κB)激活情况;酶联免疫吸附法检测海马组织肿瘤坏死因子-α(TNF-α),白细胞介素-1β(IL-1β)水平;TUNEL染色观察海马神经元凋亡情况。结果与模型组相比,T4高、低剂量组海马组织NF-κB表达减少,TNF-α、IL-1β水平降低,凋亡神经元减少,高剂量组作用更明显(P<0.01)。结论T4可能通过阻断NF-κB信号通路,发挥对拟AD样大鼠海马神经元的保护作用。Objective To explore the protective effect of tripchlorolide （T4 ） on the hippocampal neurons of the Alzheimer＇s disease（AD） rat model and its possible mechanism. Methods Dorsal hippocampus microinjection of 10 μg aggregated beta-amyloid（ Aβ）25-35 was performed by stereotaxic technique to establish the rat model of AD. Rats were divided into 5 groups ： normal group, sham operation group, model group, T4 low dose （5 μg/kg）group, T4 high dose（20 μg/kg） group. The expression of nuclear factor（ NF）-κB was detected by Western blot. The levels of tmnor necrosis factor（TNF）-α and interleukin（IL）-1β were measured by enzyme- linked immunosorbent assay, and the apoptosis of hippocampal neurons was evaluated by Tunel staining. Resuits The expression of NF-κB,the TNF-α and IL-1β level in T4 group were significantly lower than those in model group. The apoptosis of hippocampal neurons in T4 groups decreased significantly compared with model group（ P 〈 0. 05）. The T4 high dose group was especially significant（P 〈 0. 01 ）. Conclusions T, had obvious protective effect on hippocampal neurons of AD model rat, and the mechanism may be due to decreasing the levels of TNF-α and IL-1β by inhibiting NF-κB activation.

关 键 词：阿尔茨海默病 雷公藤氯内酯醇 Β淀粉样肽 核因子-ΚB 海马神经元 

分 类 号：R745.7[医药卫生—神经病学与精神病学]