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目的观察中药(平颤方)联合褪黑激素(MT)对帕金森病(PD)模型大鼠行为学和前脑纹状体细胞凋亡的影响,探讨中药联合MT治疗PD的作用及其机制。方法SD大鼠60只,分5个组:空白对照组、模型对照组、MT组、中药组、中药+MT组。模型对照组和各治疗组大鼠腹腔注射N-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)建立PD模型,用爬杆法和迷宫试验测量大鼠行为学改变和智力状况,Bax/Bcl-2免疫组织化学染色和Tunel法检测前脑纹状体凋亡细胞。结果PD大鼠出现不同程度爬杆能力下降和智力减退;与病理对照组相比,用药实验组尤其是中药+MT组大鼠行为学异常可部分或全部改善(P<0.05),前脑纹状体神经元和胶质细胞Bcl-2蛋白表达明显增强(P<0.01),Bax基因表达受抑制(P<0.01),同时前脑黑质纹状体通路细胞凋亡减少(P<0.01)。结论中药平颤方联合MT通过抗氧化应激途径,激活Bax/Bcl-2系统,调节前脑黑质纹状体通路多巴胺(DA)神经活性,抑制细胞凋亡和改善PD症状。
Objective To observe the effects of traditional Chinese medicine (Pingwei Recipe) combined with melatonin (MT) on the behavior and the apoptosis of striatum in rat model of Parkinson’s disease (PD) and to explore the role and mechanism of traditional Chinese medicine combined with MT in treating PD . Methods Sixty SD rats were divided into five groups: blank control group, model control group, MT group, TCM group and TCM + MT group. PD model was established by intraperitoneal injection of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in model control group and each treatment group, and the behavior of rats was measured by climbing rod method and maze test Changes in learning and intelligence, Bax / Bcl-2 immunohistochemical staining and Tunel method were used to detect apoptotic cells in the striatum. Results Compared with the pathological control group, the behavioral abnormalities in the experimental group, especially the traditional Chinese medicine + MT group, were partially or fully improved (P <0.05), while the forebrain pattern (P <0.01), Bax gene expression was inhibited (P <0.01), meanwhile apoptosis of neurons in glial cells was decreased (P <0.01) . CONCLUSION: MTX can activate dopaminergic neurotrophic factor (Bax / Bcl-2) system and regulate neuronal activity of dopamine (DA) in the nigrostriatal pathway of the forebrain to inhibit apoptosis and improve the symptoms of PD through anti-oxidative stress pathway.