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目的以小胶质细胞激活为特征的神经炎性反应作为帕金森病(Parkinson’sdisease,PD)一种重要的致病原因,正受到越来越多的关注。本文的目的是研究1-甲基-4-苯基-吡啶(1-methyl-4-phenyl pyridinium,MPP+)所诱导的偏侧PD大鼠模型中小胶质细胞的激活,观察雷公藤内酯作为一种小胶质细胞抑制剂对多巴胺神经元的保护作用及其对MPP+所导致的大鼠行为学异常的改善效果。方法通过黑质区域显微注射MPP+制作偏侧PD大鼠模型。分别在基线、MPP+注射后第1、3、7、14、21天时通过测定黑质区域OX-42的免疫荧光强度评定小胶质细胞的激活程度,测定酪氨酸羟化酶的表达情况评定存活多巴胺神经元的数量;通过阿朴吗啡诱导的旋转行为、前肢跨步及触须引发的不对称放置试验得分测评行为学表现。结果黑质区域MPP+注射导致小胶质细胞的激活、多巴胺神经元进行性死亡以及行为学缺陷的不断加重。雷公藤内酯可以显著抑制小胶质细胞的激活,部分阻止MPP+对多巴胺神经元的毒性,改善行为学异常。结论上述结果显示雷公藤内酯对MPP+诱导的偏侧PD大鼠模型多巴胺神经元具有保护作用,其机制可能与抑制小胶质细胞的激活有关,这为PD免疫抑制治疗提供了实验依据。
Objective The neuroinflammatory response characterized by microglial activation is an important cause of Parkinson’s disease (PD) and is receiving increasing attention. The purpose of this study was to investigate the activation of microglia in a rat model of lateralization induced by 1-methyl-4-phenylpyridinium (MPP+) and to observe triptolide as a The protective effect of several microglial inhibitors on dopamine neurons and their effect on improving the abnormal behavior of rats induced by MPP+. Methods The rat PD model was established by microinjection of MPP+ into the substantia nigra. The activation of microglia was assessed by measuring the immunofluorescence intensity of OX-42 in the substantia nigra region at baseline, MPP+ injection, 1, 3, 7, 14 and 21 days after injection, and the expression of tyrosine hydroxylase was assessed. The number of surviving dopamine neurons; behavioral performance was measured by apomorphine-induced rotational behavior, forelimb stride, and tentacles-induced asymmetry placement test scores. Results The MPP+ injection in the substantia nigra region resulted in activation of microglia, progressive death of dopaminergic neurons, and aggravation of behavioral deficits. Triptolide can significantly inhibit the activation of microglia, partially prevent the toxicity of MPP+ to dopamine neurons, and improve behavioral abnormalities. Conclusion The above results show that triptolide has a protective effect on dopamine neurons induced by MPP+ in the rat PD model. The mechanism may be related to the inhibition of microglia activation, which provides experimental basis for PD immunosuppressive therapy.