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目的:研究天芪平颤颗粒对帕金森病(PD)大鼠异动症行为学及信号转导蛋白DARPP-32、ERK磷酸化表达的影响。方法:通过6-羟基多巴(6-OHDA)立体定向至大鼠前脑内侧束建立帕金森病模型,共25只,随机分为5组,每组5只。PD组:腹腔注射0.2%维生素C液;西药组:腹腔注射左旋多巴甲酯29 d;中药小剂量组、中剂量组、大剂量组:给予左旋多巴甲酯基础上分别加用不同剂量天芪平颤颗粒;另设假手术组为对照组(n=5)。评估不同剂量天芪平颤颗粒对PD模型大鼠运动并发症的行为学影响,并用免疫组织化学方法检测大鼠纹状体区磷酸化的DARPP-32和ERK表达情况。结果:天芪平颤颗粒能减少左旋多巴制剂产生的剂峰旋转次数。免疫组化显示,与PD组大鼠比较,西药组磷酸化DARPP-32(Thr75)明显降低,中剂量组和大剂量组均未出现明显的降低(P>0.05)。与PD组磷酸化ERK1/2比较,左旋多巴长期治疗后,磷酸化ERK1/2表达升高,中剂量组和大剂量组表达量均未出现明显上升(P>0.05)。结论:天芪平颤颗粒可以减少PD大鼠剂峰异动行为,可能通过DARPP-32(Thr75)及ERK1/2磷酸化,达到调节胞内异常信号转导的功能。
Objective: To investigate the effect of Tianqi Ping on the behavior and the phosphorylation of DARPP-32 and ERK in the Parkinson disease (PD) rats. Methods: Parkinson’s disease model was established by 6-hydroxydopamine (6-OHDA) stereotaxis to medial forebrain of rats. A total of 25 rats were randomly divided into 5 groups with 5 rats in each group. PD group: intraperitoneal injection of 0.2% vitamin C solution; Western medicine group: intraperitoneal injection of levodopa methyl ester for 29 days; Chinese medicine small dose group, medium dose group, high dose group: given levodopa methyl ester were added with different doses Tianqi Ping fibril particles; another sham operation group for the control group (n = 5). To evaluate the effect of different doses of Tianqi Ping on the behavioral complications of PD rats and the phosphorylation of DARPP-32 and ERK in rat striatum were detected by immunohistochemistry. Results: Tianqi Ping fibrillation particles can reduce the number of peak rotation of levodopa preparation. Immunohistochemistry showed that phosphorylation of DARPP-32 (Thr75) in western medicine group was significantly lower than that in PD group, and no significant decrease was found in middle dose group and high dose group (P> 0.05). Compared with phosphorylated ERK1 / 2 in PD group, the expression of phosphorylated ERK1 / 2 increased after long-term treatment of levodopa, but there was no obvious increase in the expression of ERK1 / 2 in middle dose group and high dose group (P> 0.05). CONCLUSION: Tianqi Pingbu granule can reduce the peak-to-peak abnormality of PD rats, and may regulate the abnormal signal transduction via DARPP-32 (Thr75) and ERK1 / 2 phosphorylation.