脂多糖诱导小胶质细胞激活与多巴胺能神经元毒性作用关系的研究  

Neurotoxicity effect of activated microglia induced by lipopolysaccharide(LPS) on dopaminergic neurons.

作　　者：叶钦勇[1] 徐评议[1] 刘焯霖[1] 徐浩文[1] 朱蔚文[1] 谢安木[1] 杨海华[1] 

机构地区：[1]中山大学附属第一医院神经内科,广州市510080

出　　处：《中华老年医学杂志》2005年第7期537-540,共4页Chinese Journal of Geriatrics

基　　金：国家自然科学基金(No:30370509);留学回国人员基金((No:2003406)

摘　　要：目的探讨脂多糖(LPS)诱导小胶质细胞(Mic)激活规律与黑质多巴胺(DA)能神经元变性的关系。方法分别于LPS注入大鼠脑黑质后7d、14d、30d观察大鼠行为学改变,并采用免疫组织化学及原位杂交等方法观察Mic的激活情况以及酪氨酸羟化酶(TH)神经元的表达。结果行为学改变表现为7d仅引起轻度的旋转行为〔(85±13)圈/30min〕,至14d时旋转次数增多〔(121±17)圈/30min〕,30d时达高峰〔(295±21)圈/30min〕;7dMic部分激活,14d时大部分激活,30d时Mic已全部活化;TH阳性细胞数7d时轻度减少〔(135.22±12.11)PU〕,14d时进一步减少〔(21.54±4.89)PU〕,30d时已罕见〔(11.31±2.56)PU〕。THmRNA的表达规律与其一致,分别为(60.69±8.47)PU、(39.87±7.03)PU、(14.23±3.51)PU。结论Mic的激活是构成PD炎症损伤机制的重要环节。Objective To explore the relationship between the activities of microglia induced by LPS and the degeneration of dopaminergic neurons. Methods At the different survial time(7,14,10 d) after injection of LPS in the substantia nigra (SN) of rats, the behavior was measured, and the tyrosine hydroxylase(TH) positive neurons and OX-42-positve microglias were observed by immunohistochemistry and insitu hybridization. Results The slightly rotational behavior was observed on the 7d (85±13) r/30min, the times increased on the 14d(121±17) r/30 min, the highlight was in the 30d(295±21) r/30 min.The microglias were activated partly on the 7d, in majority on the 14 d, totally on the 30 d. The TH positve neurons decreased gently on the 7 d〔(135.22±12.11) PU〕, markedly on the 14d〔(21.54±4.89) PU〕, almost all disappeared on the 30 d〔(11.31±2.56) PU〕. The expression of TH mRNA was consistent with TH positve neurons, the value of PU were 60.69±8.47, 39.87±7.03 and 14.23±3.51 respectively. Conclusions The activation of microglias is the key to the inflammation mechanism of PD′s pathogenesis.

关 键 词：多巴胺能神经元 小胶质细胞激活 脂多糖诱导 毒性作用 脂多糖(LPS) 多巴胺(DA) 行为学改变 酪氨酸羟化酶 免疫组织化学 神经元变性 Mic 原位杂交 旋转行为 表达规律 mRNA 重要环节 损伤机制 脑黑质 c部分 细胞数 大鼠 轻度 

分 类 号：R742.5[医药卫生—神经病学与精神病学] R338[医药卫生—临床医学]