Wang Yanqin, Zhao Weilin, Li Ge, Chen Jinhu, Guan Xin, Chen Xi, Guan Zhenlong
Department of Physiology, College of Life Science, Hebei Normal University, Shijiazhuang, Hebei 050024, China.
Human Movement Science, Hebei Institute of Physical Education, Shijiazhuang, Hebei 050041, China.
PPAR Res. 2017;2017:4089214. doi: 10.1155/2017/4089214. Epub 2017 Mar 5.
The aim of the present study was to gain insight into the neuroprotection effects and mechanism of thiazolidinedione pioglitazone in both and MPP/MPTP induced PD models. experimental results showed that oral treatment of pioglitazone resulted in significant improvements in behavior symptoms damaged by MPTP and increase in the survival of TH positive neurons in the pioglitazone intervention groups. In addition, oral treatment of pioglitazone increased the expression of peroxisome proliferator-activated receptor- coactivator of 1 (PGC-1) and increased the number of mitochondria, along with an observed improvement in mitochondrial ultrastructure. From studies, 2,4-thiazolidinedione resulted in increased levels of molecules regulated function of mitochondria, including PGC-1, nuclear respiratory factor 1 (NRF1), NRF2, and mitochondria fusion 2 (Mfn2), and inhibited mitochondria fission 1 (Fis1). We show that protein levels of Bcl-2 and ERK were reduced in the MPP-treated group compared with the control group. This effect was observed to be reversed upon treatment with 2,4-thiazolidinedione, as Bcl-2 and ERK expression levels were increased. We also observed that levels of the apoptotic protein Bax showed opposite changes compared to Bcl-2 and ERK levels. The results from this study confirm that pioglitazone/2,4-thiazolidinedione is able to activate PGC-1 and prevent damage of dopaminergic neurons and restore mitochondria ultrastructure through the regulation of mitochondria function.
本研究的目的是深入了解噻唑烷二酮类药物吡格列酮在6-羟基多巴胺（6-OHDA）和1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导的帕金森病（PD）模型中的神经保护作用及其机制。实验结果表明，吡格列酮口服治疗可显著改善MPTP损伤的行为症状，并增加吡格列酮干预组中酪氨酸羟化酶（TH）阳性神经元的存活。此外，吡格列酮口服治疗可增加过氧化物酶体增殖物激活受体γ共激活因子1（PGC-1）的表达，增加线粒体数量，并观察到线粒体超微结构有所改善。从细胞研究来看，2,4-噻唑烷二酮可导致线粒体调节功能分子水平升高，包括PGC-1、核呼吸因子1（NRF1）、NRF2和线粒体融合蛋白2（Mfn2），并抑制线粒体分裂蛋白1（Fis1）。我们发现，与对照组相比，MPP处理组中Bcl-2和细胞外信号调节激酶（ERK）的蛋白水平降低。在用2,4-噻唑烷二酮治疗后，这种效应被逆转，因为Bcl-2和ERK的表达水平增加。我们还观察到，凋亡蛋白Bax的水平与Bcl-2和ERK的水平呈现相反的变化。本研究结果证实，吡格列酮/2,4-噻唑烷二酮能够激活PGC-1，通过调节线粒体功能来预防多巴胺能神经元损伤并恢复线粒体超微结构。
