Department of Neurology, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China.
Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221002, Jiangsu, China.
Biomed Res Int. 2019 Mar 5;2019:6843265. doi: 10.1155/2019/6843265. eCollection 2019.
The aim of this study was to investigate the effect of minocycline in rats with rotenone-induced Parkinson's disease (PD). The open field test was performed to determine the motor ability of the rats. Double immunofluorescence staining was used to detect the expression of tyrosine hydroxylase (TH) and Nurr1 in the substantia nigra (SN) of rats. The relative protein levels of TH, Nurr1, and the total- and phosphorylated-cAMP-response element binding protein (CREB) were determined by western blot analysis. The production of reactive oxygen species (ROS) and nitric oxide (NO) was detected by commercial kits. After exposure to rotenone for 28 days, rats exhibited decreased ambulation and rearing frequency and prolonged immobility time with loss of TH positive neurons in the SN. The phosphorylation levels of CREB and Nurr1 expression decreased significantly accompanied with the release of ROS and NO. Minocycline alleviated the motor deficits of rats lesioned by rotenone and elevated the expression of TH, as well as suppressing the release of ROS and NO in the SN. That was in line with the elevated phosphorylation levels of CREB and Nurr1 expression. In conclusion, our present study showed minocycline protected against neurotoxicity in a rotenone-induced rat model of PD, which was correlated with upregulation of Nurr1.
本研究旨在探讨米诺环素对鱼藤酮诱导的帕金森病（PD）大鼠的作用。通过旷场实验来测定大鼠的运动能力。采用双重免疫荧光染色法检测大鼠黑质（SN）中酪氨酸羟化酶（TH）和 Nurr1 的表达。通过 Western blot 分析测定 TH、Nurr1、总及磷酸化环磷酸腺苷反应元件结合蛋白（CREB）的相对蛋白水平。通过商业试剂盒检测活性氧（ROS）和一氧化氮（NO）的产生。在暴露于鱼藤酮 28 天后，大鼠出现运动减少、站立次数减少和静止时间延长，SN 中 TH 阳性神经元丢失。CREB 磷酸化水平和 Nurr1 表达显著下降，同时伴随着 ROS 和 NO 的释放增加。米诺环素减轻了鱼藤酮损伤大鼠的运动障碍，提高了 TH 的表达，并抑制了 SN 中 ROS 和 NO 的释放。这与 CREB 和 Nurr1 表达的磷酸化水平升高一致。总之，本研究表明米诺环素对鱼藤酮诱导的 PD 大鼠的神经毒性具有保护作用，这与 Nurr1 的上调有关。
