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目的:观察使用天芪平颤颗粒后,大鼠左旋多巴诱发的运动并发症的行为学及纹状体β-arrestin1表达的变化。方法:通过脑立体定向仪定向至大鼠前脑内侧束,注射6-OHDA建立帕金森病模型(n=25),并随机分为五组。PD对照组(n=5,腹腔注射0.2%维生素C液29 d),西药组(连续腹腔注射50 mg.kg-1左旋多巴甲酯和25 mg.kg-1苄丝肼29 d),中药大剂量组、中药中剂量组、中药小剂量组(在给予左旋多巴甲酯/苄丝肼的基础上分别加用中药(天芪平颤颗粒)29 d)。观察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,通过免疫组织化学方法和Western blotting法检测不同处理组大鼠纹状体区β-arrestin1蛋白的表达情况。结果:PD大鼠长期使用左旋多巴出现类似于人类LID行为表现。免疫组化结果显示长期左旋多巴的使用使β-arrestin1表达进行性减少,天芪平颤颗粒能抑制β-arrestin1阳性细胞指数的减少,其中中剂量组β-arrestin1阳性细胞指数为(3.67±0.56)×104比PD大鼠增多(P<0.01)。Western blot结果显示,与长期使用左旋多巴的大鼠(65.44±6.68)%比较,中剂量组和大剂量组β-arrestin1表达量分别为(73.62±3.82)%和(72.56±6.66)%,明显升高,差异有统计学意义(P<0.05)。结论:天芪平颤颗粒通过增加β-arrestin1蛋白表达量,减少了左旋多巴长期用药引起的PD异动症的发生。
OBJECTIVE: To observe the behavioral changes and the expression of β-arrestin1 in striatum induced by levodopa in rats after using Tianqipingtong granules. Methods: The brain was oriented to the medial forebrain bundle of rats by injection of 6-OHDA. Parkinson’s disease model was established (n = 25) and divided into five groups at random. PD control group (n = 5, intraperitoneal injection of 0.2% vitamin C solution for 29 days), western medicine group (continuous intraperitoneal injection of 50 mg.kg-1 levodopa methyl ester and 25 mg.kg-1 benserazide for 29 days) Chinese medicine large dose group, medium dose group, traditional Chinese medicine small dose group (given levodopa methyl / benserazide based on the use of traditional Chinese medicine (Tianqi Ping fibrillation particles) 29 d). To observe the effect of different doses of Tianqipingtong granules on the behavioral complications of PD model rats. The expression of β-arrestin1 protein in striatum of different treatment groups was detected by immunohistochemistry and Western blotting. RESULTS: Long-term use of levodopa in PD rats showed similar behavior to human LIDs. The results of immunohistochemistry showed that the use of long-term levodopa reduced the expression of β-arrestin1 progressively, and Tianqi Tablet could inhibit the decrease of β-arrestin1 positive cells index. The β-arrestin1 positive index of medium dose group was (3.67 ± 0.56) × 104 than PD rats (P <0.01). The results of Western blot showed that the expression of β-arrestin1 was (73.62 ± 3.82)% and (72.56 ± 6.66)% in the middle-dose group and the high-dose group, respectively, compared with 65.44 ± 6.68% Was significantly higher, the difference was statistically significant (P <0.05). Conclusion: Tianqi Pulmonary Granule can reduce the incidence of PD dyskinesia caused by long-term administration of levodopa by increasing the expression of β-arrestin1.