止颤颗粒联合美多芭对1-甲基-4-苯基-1,2,3,6-四氢吡啶引起亚急性帕金森病模型小鼠的药效学研究

Pharmacodynamics of Zhichan Granule combined with Madopa on subacute Parkinson's disease model mice induced by methylphenyltetrahydropyridine

目的联合应用止颤颗粒和美多芭,观察止颤颗粒是否具有增强美多芭治疗帕金森病(PD)的作用。方法采用经典的1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱发小鼠亚急性PD模型,105只小鼠,随机分为7组,每组15只,分别为对照组、模型组、止颤颗粒低剂量(3.5 g/kg)+美多芭(50 mg/kg)组、止颤颗粒中剂量(9.0 g/kg)+美多芭(50 mg/kg)组、止颤颗粒高剂量(22 g/kg)+美多芭(50 mg/kg)组、止颤颗粒(22 g/kg)组、美多芭(50 mg/kg)组。采用转棍法和爬杆法检测各组小鼠的行为学指标,采用HPLC法测定纹状体中多巴胺(DA)水平、免疫组化法检测黑质多巴胺神经元数量。结果止颤颗粒低剂量+美多芭组与美多芭组相比,纹状体内DA的水平、TH阳性神经元数目均明显提高,而且PD模型小鼠行为学障碍改善作用较明显。与模型组相比,止颤颗粒组小鼠的行为学障碍改善作用较明显。结论止颤颗粒可增强美多芭的疗效,具有一定的神经保护作用,止颤颗粒低剂量与美多芭合用可适当减少美多芭的用量。

Objective To study whether Zhichan Granule could enhance the effect of Madopar for treating Parkinson＇s disease （PD）. Methods Subacute PD model induced by methylphenyltetrahydropyridine （MPTP） in mice was adopted and 105 male C57 mice were randomly divided into seven groups with 15 in each group, they were control group, model group, Zhichan Granule in low dose （3.5 g/kg） medium dose （9.0 g/kg）, and high dose （22 g/kg） combined with DOPA （50 mg/kg） groups, Zhichan Granule （22 g/kg）, and Madopar （50 mg/kg） groups, respectively. Behaviors of mice in each group were observed by rollover and pole climbing method. The content of striatum dopamine and the number of dopamine neurons of substantia nigra were detected by HPLC and immunohistochemical method. Results Compared with the Madopar group, the content of striatum dopamine and the number of dopamine neurons of substantia nigra were significantly increased in the group of low-dose Zhichan Granule combined with Madopar, and the behaviors were significantly improved. Compared with the model group, the behaviors were significantly improved in the group of Zhichan Granule. The results indicated that Zhichan Granule in a low-dose could enhance the effect of Madopar for treating PD, resulting in reduction of the dose of Madopar to a certain degree. Conclusion Zhichan Granule could enhance the effect of Madopar for treating PD, which has nerve protective effect.