Rapamycin protects the mitochondria against oxidative stress and apoptosis in a rat model of Parkinson's disease
Rapamycin protects the mitochondria against oxidative stress and apoptosis in a rat model of Parkinson's disease
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DOI：
10.3892/ijmm.2013.1280
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发表时间：
2013-04-01
影响因子：
5.4
通讯作者：
Gu, Zhenlun
中科院分区：
文献类型：
--
作者：
Jiang, Jianhua;Jiang, Juean;Gu, Zhenlun
帕金森病（PD）是一种神经退行性疾病，氧化应激和线粒体功能障碍是神经元凋亡的主要原因。雷帕霉素在减少氧化应激和保护线粒体方面起着至关重要的作用。然而，其在帕金森病中的保护作用尚未完全阐明。在这项研究中，我们报告了雷帕霉素预处理可以改善PD大鼠模型的行为，防止多巴胺能神经元的丢失，并减轻线粒体超微结构损伤。与用载体预处理的PD大鼠相比，经雷帕霉素预处理的PD大鼠的过氧化物水平较低，抗氧化活性较高。此外，与载体预处理相比，雷帕霉素预处理显著提高了抗凋亡标志物的表达，降低了促凋亡标志物的水平。综上所述，我们的研究结果表明，雷帕霉素在6-羟多巴胺（6-OHDA）诱导的PD大鼠模型中降低了氧化应激，减轻了线粒体损伤，这可能随后有助于其抗凋亡作用。雷帕霉素在帕金森病大鼠模型中表现出神经保护作用的能力可能与其抗氧化能力有关。
Parkinson's disease (PD) is a neurodegenerative disease, in which oxidative stress and mitochondrial dysfunction are responsible for neuronal apoptosis. Rapamycin plays a crucial role in reducing oxidative stress and protecting the mitochondria. However, its protective role in PD has not yet been fully elucidated. In this study, we report that pre-treatment with rapamycin provides behavioral improvements, protects against the loss of dopaminergic neurons, and alleviates mitochondrial ultrastructural injuries in a rat model of PD. Peroxide levels were lower and antioxidant activities were higher in PD rats pre-treated with rapamycin compared to the PD rats pre-treated with the vehicle. Furthermore, pre-treatment with rapamycin significantly elevated the expression of anti-apoptotic markers and reduced the levels of pro-apoptotic markers compared to pre-treatment with the vehicle. In conclusion, our results demonstrated that rapamycin reduced oxidative stress and alleviated mitochondrial injuries in the 6-hydroxydopamine (6-OHDA)-induced rat model of PD, which may subsequently contribute to its anti-apoptotic effects. The ability of rapamycin to exhibit neuroprotection in a rat model of PD may be related to its antioxidant capabilities.