目的 观察蛋白酶体抑制剂Lactacystin诱导大鼠黑质胶质细胞的变化、炎性介质NF-κB的表达.方法 采用立体定向术将蛋白酶体抑制剂Lactacystin 10μg注射至大鼠黑质部位,免疫组织化学法观察黑质区多巴胺(DA)能神经元、小胶质细胞、星形胶质细胞的变化,炎性介质核转录因子κB(NF-κB)的表达.结果 注射Lactacystin 3周,阿朴吗啡腹腔注射后出现典型旋转行为;8周后实验组大鼠损毁侧黑质酪氨酸羟化酶(TH)阳性细胞数明显减少,黑质小胶质细胞及星形胶质细胞的数量均增加,NF-κB表达增强.结论 蛋白酶体抑制剂Lactacystin能激活大鼠黑质小胶质细胞及星形胶质细胞,诱导炎性介质表达.%Objective To investigate the changes of glial cells and the expression of inflammatory mediators in the substantia nigra of rats with Parkinson's disease induced by the proteasome inhibitor lactacystin. Methods After stereotaxic unilateral injection of lactacystin (10μg) ,a selective proteasome inhibitor , into the substantia nigral pars compacta of rats,the spontaneous and apomorphine-induced contralateral behavior of rats was observed. Changes of dopaminergic neurons and glial cells and expression of inflammatory mediators nuclear factor-κB (NF-κB) in substantia nigra were investigated by immunohistochemistry. Results On day 14, apomorphineinduced contralateral behavior was notably observed in rats of the lactacystin group. After 8 weeks, the number of tyrosine hydroxylase (TH)-positive cells in the injected side of the substantia nigra of the lactacystin group rats was significantly reduced. The number of microglial cells and astrocytes were significantly increased in the lactacystin group; and the optical density values of NF-κB in the substantia nigra were increased obviously. Conclusion The proteasome inhibitor lactacystin may cause microglia and astrocyte activation in the substantia nigra of rats and induce the expression of certain inflammatory mediators.
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