雷公藤氯内酯醇对大鼠海马背侧注射Aβ_(25-35)后胶质细胞及p38MAPK激活的抑制作用  

Inhibitory action of tripchlorolide on activation of gliacyte and p38MAPK induced by Aβ_(25- 35)injected into hippocampus of rats

作　　者：王元伟[1,2] 郑关毅[1] 陈晓春[1] 张静[1] 黄天文[1] 叶洪[1] 潘晓东[1] 

机构地区：[1]福建医科大学附属协和医院福建省老年医学研究所,福建福州350001 [2]江苏省沭阳县人民医院,江苏沭阳223600

出　　处：《中国药理学通报》2014年第1期108-113,共6页Chinese Pharmacological Bulletin

基　　金：福建省卫生厅中医药重点课题(No WZZ10604);福建省自然科学基金资助项目(No 2009J06015)

摘　　要：目的探讨雷公藤氯内酯醇(T4)对海马背侧注射Aβ25-35后模型大鼠神经元损伤的保护作用及可能机制。方法通过Nissl和TUNEL染色法检测阳性神经元数量,采用免疫组化、蛋白印迹法观察ox-42、GFAP和p-p38MAPK的表达;ELISA法检测TNF-α、IL-1β的含量。结果 T4干预后(7 d),ox-42、GFAP、p-p38MAPK的表达减弱,Nissl阳性神经元增多,TUNEL阳性神经元减少,TNF-α、IL-1β的含量降低。结论 T4保护注射Aβ25-35后大鼠海马神经元损伤的机制可能与抑制小胶质细胞、星形胶质细胞和p38MAPK的激活有关。Aim To investigate the protective effect of tripchlorolide（T4 ） on neuronal injury induced by in- jecting Aβ25-35 into dorsal hippocampus in rats and its possible mechanism. Methods The model was estab- lished by using stereotaxic technique to inject 10 Ixg aggregated Aβ25-35 into dorsal hippocampus in rats. Rats were treated with different doses of T4. The ex- pression of ox-42, GFAP and p-p38MAPK were ob- served by immunohistochemistry or Western blot, the levels of TNF-α and IL-1β were measured by ELISA, and neuronal injury of hippocampus was evaluated by TUNEL and Nissl staining. Results After injection of Aβ25-35, the expression of ox-42, GFAP and p- p38MAPK increased and achieved the peak on 7th day, and the levels ofTNF-α , IL-1βsignificantly increased too. Meanwhile, the apoptosis of hippocampal neurons was gradually increased and peaked on 7th day. After treatment with T4, the expregsion of glia- cyte, p-p38MAPK, the levels of TNF-α and IL-1β, and the apoptosis of hippocampal neurons were signifi- cantly decreased. The dose of 20 μg effective. Conclusion The possible · kg-1 was more protective mechanism of T4 may be associated with decreasing the levels of cytokines by inhibiting the activation of gliacyte and p38MAPK induced by injecting Aβ25-35 into hippocampus.

关 键 词：阿尔采末病 雷公藤氯内酯醇 Β淀粉样肽 磷酸化 P38MAPK 小胶质细胞 星型胶质细胞 海马神经元 

分 类 号：R-332[医药卫生] R284.1