红景天甙通过抑制肿瘤坏死因子-α表达对帕金森模型小鼠多巴胺能神经元的保护作用

摘要

目的；研究红景天甙对1-甲基-4苯基-1,2,3,6-四氢吡啶(MPTP)诱发的帕金森病(PD)小鼠模型黑质区多巴胺能神经元保护作用及其可能机制.方法:采用MPTP制备PD小鼠模型.将小鼠随机分为MPTP模型组、红景天甙组和对照组.对各组动物进行行为学观察,采用免疫组织化学、免疫蛋白印迹和免疫荧光双标法,观察各组小鼠中脑黑质区酪氨酸羟化酶(TH)、肿瘤坏死因子-α(TNF-α)阳性细胞表达和蛋白水平的变化；观察红景天甙对上述变化的影响.结果:与对照组小鼠相比,模型组小鼠出现典型的PD样症状.MPTP模型组黑质区(SN) TH阳性神经元和蛋白表达水平较对照组减少约为40％和60％,TNF-α阳性细胞和蛋白表达水平增加；经红景天甙处理后,上述变化均减轻.结论:红景天甙可在一定程度上阻抑MPTP诱导的PD模型小鼠黑质区多巴胺能神经元的丢失；其神经保护机制可能与抑制TNF-α的表达有关.%Objective:To investigate the neuroprotective effects of salidroside on dopominergic neurons of Parkinson's disease (PD) mouse model induced by l-methy-4-methy-l,2,3,6-tetrahydyridine (MPTP). Methods:C57BL/6N mice were treated with MPTP to establish PD model. Healthy C57BL/6N mice were randomly divided into 3 groups: MPTP model group, salidroside intervent group and control gourp. The behavior was observed. The changes of TH and TNF-α-positive cells, and protein expression levels of TH and TNF-a in the SN of the midbrain were detected with immunohistochemistry, Western blotting and double-labeling immunofluorescence assay. Results:Compared with the mouse in the control group, the PD mouse exhibited typical symptoms of PD. The number of TH-positive cell neurons and protein expression level of TH in the model group were reduced in the substantia nigra by about 40% and 60 %. The number of TNF-α- positive cell neurons and protein expression level of TNF-a were markedly increased. After giving salidroside, the above changes were obviously alleviated. Conclusion:Salidroside could mitigate the loss of dopominergic neurons in the PD mouse model induced by MPTP. The mechanism of neuroprotective effect may be related to inhibit the expression of TNF-a.