脂多糖诱发大鼠黑质多巴胺能神经元变性

Degeneration of Substantial Nigral Dopaminergic Neurons Induced by Lipopolysaccaride

目的 :观察脂多糖 (Lipopolysaccharide,LPS)对黑质多巴胺 (DA)能神经元的毒性作用 ,探讨帕金森病 (PD)发病机制。方法 :脑立体定位注射LPS入大鼠脑黑质后 ,采用酪氨酸羟化酶 (Tyrosinehydroxylase,TH)免疫组织化学染色 ,观察不同剂量LPS和 5 μgLPS注射后不同时间点黑质DA能神经元的损伤状况。结果 :0 1～ 10 μgLPS注射后14d ,导致TH+ 细胞数下降分别为 5 %、15 %、2 0 %、4 5 %、96 %和 99% ;5 μgLPS注射后与对照组相比 ,TH+ 细胞数3d后开始下降 ,14d明显减少 ,仅为 5 % ,30d后基本消失。结论 :LPS能诱导黑质DA能神经元变性 ,呈剂量和时间依赖性。

Objective:To explore the degeneration effects of lipopolysaccharide (LPS) on substantial nigral dopaminergic (DA) neurons and the pathogenesis of Parkinson diseases. Methods:LPS was stereotaxically infused into substantial nigra (SN). At different concentrations of LPS and at different time points with 5 μg LPS injection, the damage of the substantial nigral DA neurons was observed by using tyrosine hydroxylase (TH) immunohistochemical staining. Results:14 days after injection of 0.1 to 10 μg LPS, TH + cells were decreased by 5 %, 15 %, 20 %, 45 %, 96 % and 99 %, respectively. After injection of 5 μg LPS, as compared with control group, TH + cells began to decrease at 3rd day and obviously decreased at 14 day, only 5 % of total cells, and almost disappeared 30 days later. Conclusion:LPS could induce the degeneration of DA neurons in the SN in a dosage and time dependent manner.