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目的:观察龟羚帕安丸对帕金森病(PD)大鼠行为学及中脑黑质细胞孤儿核受体相关因子1(Nurr1)、酪氨酸羟化酶(TH)以及其mRNA表达的影响。方法:采用6-OHDA注射法建立PD大鼠模型,造模成功大鼠随机分为模型组,美多芭组(10mg/kg),龟羚帕安丸4g/kg、2g/kg、1g/kg组,假手术组、模型组给予等容积生理盐水,连续灌胃给药30天。观察各组大鼠旋转圈数变化,免疫组织化学法检测中脑黑质Nurr1、TH蛋白表达,原位杂交法检测中脑黑质Nurr1mRNA、THmRNA表达。结果:与假手术组比较,模型组Nurr1、TH蛋白及其mRNA表达均显著降低;与模型组比较,各治疗组Nurr1、TH蛋白及其mRNA表达均明显升高,旋转圈数显著降低;起效剂量为1g/kg,剂量范围为1g/kg~4g/kg。结论:龟羚帕安丸通过提高Nurr1表达,进而上调下游靶基因TH的表达,从而诱导神经干细胞分化为成熟多巴胺能神经元,并最终转化为神经递质DA,可能是龟羚帕安丸治疗PD的作用机制之一。
Objective: To observe the effects of Guiling Pan’an Pill on the behavior and the expression of Nurr1, Tyr and its mRNA in orbital nucleus of Parkinson’s disease (PD) rats . Methods: The rat model of PD was established by injection of 6-OHDA. The rats were randomly divided into model group, metoprolol group (10mg / kg), Guilingpaan pill 4g / kg, 2g / kg, Group, sham operation group, model group were given equal volume of normal saline, continuous oral administration for 30 days. The number of rotations in each group was observed. The expression of Nurr1 and TH protein in substantia nigra was detected by immunohistochemistry. The expression of Nurr1 mRNA and THmRNA in substantia nigra was detected by in situ hybridization. Results: Compared with the sham operation group, the protein and mRNA expression of Nurr1 and TH in the model group decreased significantly. Compared with the model group, the protein and mRNA expression of Nurr1 and TH in each treatment group were significantly increased and the number of revolutions significantly decreased. Effective dose of 1g / kg, the dose range of 1g / kg ~ 4g / kg. Conclusion: Guiling Pan’an pill can induce neural stem cells to differentiate into mature dopaminergic neurons by increasing Nurr1 expression and then up-regulating the expression of downstream target gene TH, and eventually converting to neurotransmitter DA, which may be related to the treatment of PD One of the mechanisms.