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目的:观察蛋白酶体抑制剂Lactacystin诱导大鼠黑质小胶质细胞的变化及炎性介质的表达。方法:采用立体定向术将不同剂量(2μg,10μg)的蛋白酶体抑制剂Lactacystin注射至大鼠黑质部位,免疫组织化学法观察黑质区多巴胺能神经元和小胶质细胞的变化及炎性介质环氧化酶-2(COX-2)、核转录因子κB(NF-κB)的表达。结果:注射不同剂量Lactacystin14d,阿扑吗啡腹腔注射后2μgLactacystin组大鼠无旋转行为,10μgLacta-cystin组出现典型旋转行为;8周后2μgLactacystin组大鼠损毁侧黑质酪氨酸羟化酶(TH)阳性细胞数明显减少,2μg和10μgLactacystin组黑质小胶质细胞数量均增加,炎性介质COX-2、NF-κB表达均增强。结论:蛋白酶体抑制剂Lactacystin能激活大鼠黑质小胶质细胞,诱导炎性介质表达。
Objective: To observe the changes of rat substantia nigra microglia and the expression of inflammatory mediators induced by proteasome inhibitor Lactacystin. Methods: Lactacystin was injected into substantia nigra at different doses (2μg, 10μg) by stereotaxic method. The changes of dopaminergic neurons and microglia in the substantia nigra were observed by immunohistochemistry Expression of COX-2 and NF-κB. RESULTS: After injection of different doses of Lactacystin14d, 2μgLactacystin group had no rotation behavior after injection of apomorphine, and 10μgLacta-cystin group showed typical rotation behavior. After 8 weeks, the damage tyrosine hydroxylase (TH) The number of positive cells decreased obviously. The number of substantia nigra microglia in 2μg and 10μg Lactacystin group increased, while the expressions of COX-2 and NF-κB in inflammatory mediators increased. Conclusion: The proteasome inhibitor Lactacystin can activate rat substantia nigra microglial cells and induce the expression of inflammatory mediators.