雷帕霉素对老龄帕金森病模型小鼠线粒体损伤的改善作用

发布时间：2018-02-11 20:21

本文关键词： 雷帕霉素老龄帕金森病线粒体　出处：《中国医科大学学报》2017年09期 　论文类型：期刊论文

【摘要】：目的探讨雷帕霉素(RAPA)对老龄帕金森病(PD)模型小鼠线粒体损伤的改善作用。方法选用12月龄快速老化小鼠P8系(SAMP8)40只,随机分为空白组、模型组、RAPA低剂量组、中剂量组和高剂量组。对模型组、RAPA低、中、高剂量组小鼠皮下注射1-甲基-4-苯基~(-1),2,3,6-四氢吡啶(MPTP)制成PD模型小鼠。RAPA低、中、高剂量组从制模前7 d、制模过程中5 d、制模后7 d分别按1、2、4 mg·kg~(-1)·d~(-1)持续给予RAPA;空白组、模型组同法注射等体积无菌生理盐水。给药结束后对各组小鼠进行行为学检测及黑质多巴胺(DA)含量检测,分析各组小鼠线粒体跨膜电位及线粒体复合物活性的差异。结果与空白组小鼠相比,模型组小鼠的行为学成绩、黑质DA含量、线粒体跨膜电位和复合物Ⅰ活性均显著下降(P0.05);与模型组小鼠相比,RAPA不同剂量组小鼠的上述指标均显著改善(P0.05);不同剂量RAPA组之间无统计学差异。结论 RAPA对老龄PD模型小鼠具有保护作用,其机制可能与保护其线粒体损伤有关。
[Abstract]:Objective to investigate the effect of rapamycin (Rapa) on mitochondrial damage in aged Parkinson's disease (PD) mice. Methods Forty 12-month-old mice with rapid aging P8 strain SAMP8A were randomly divided into blank group, model group and low dose group of RAPA. Middle dose and high dose groups. The mice in model group were treated with low RAPA, medium and high dose groups were subcutaneously injected with 1-methyl-4-phenyl-pyridyl (1-methyl-4-phenyl) and 6-tetrahydropyridine (MPTPTP) to make PD model mice. In the high dose group, RAPA was given continuously 7 days before and 5 days after making the model, and 7 days after making the model, respectively, according to 1 ~ 2mg 路kg ~ (-1) 路d ~ (-1) 路d ~ (-1)), the blank group was treated with RAPA, and the control group was treated with RAPA. The rats in the model group were injected with the same volume of aseptic saline. After administration, the behavior and the content of dopamine in the substantia nigra were measured in each group. The difference of mitochondrial transmembrane potential and mitochondrial complex activity in each group was analyzed. Results compared with the control group, the behavioral scores and DA content of the substantia nigra in the model group were higher than those in the control group. The mitochondrial transmembrane potential and the activity of complex I decreased significantly (P 0.05), compared with the model group, the above indexes were significantly improved in mice with different doses of rapa, and there was no significant difference between different dose RAPA groups. Conclusion RAPA has no significant difference in aging PD. Model mice have protective effects, The mechanism may be related to the protection of mitochondria damage.
【作者单位】：河北医科大学第一医院神经内科河北省脑老化与认知神经科学实验室;
【基金】：河北省医学科学研究重点课题计划(20160202) 河北医科大学第一医院“星火”青年科研项目(XH201711)
【分类号】：R-332;R742.5

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