天芪平颤颗粒通过β-arrestin1预防PD运动并发症的机制研究  

Research on TCM Preventing Levodopa-induced Dyskinesia in Parkinson's Disease by β-arrestin1

作　　者：吴娜[1] 宋璐[1] 杨新新[1] 魏江磊[2] 刘振国[1] 

机构地区：[1]上海交通大学医学院附属新华医院神经内科,上海200092 [2]上海中医药大学附属曙光医院急诊科,上海200032

出　　处：《中华中医药学刊》2013年第8期1595-1598,I0004,共5页Chinese Archives of Traditional Chinese Medicine

基　　金：国家自然科学基金资助项目(81071025;81171203);上海市科委基础研究重点资助项目(09JC1411000);上海市教委科研创新重点资助项目(10ZZ72)

摘　　要：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 explore the variation of between levodopa - induced dyskinesia （LID） and β- arrestinl after treated with TCM （Traditional Chinese Medicine） in striatum. Methods： The hemi -parkinsonian rat model was produced by steretaxically injecting 6 - OHDA to fight medial forebrain bundle（MFB） , and was randomly divided into five groups： PD control group （ n = 5, intraperitoneal injection with vitamin C） , levodopa group （ n = 5, intraperitoneal injection with levodopa for 29 d）, TCM - low, TCM - medium, TCM - high group （ n = 5 respectively, intraperitoneal injection with levodopa for 29 d after given TCM by garage） and another 5 rats were served as control group （ sham - operation group, n = 5 ）. The behaviors of LID rats treated with TCM of different doses were observed, and the expression of β - arrestinl in the striate of rats was detected by Immunoehemicalhistory and Western blotting. Results ： After levodopa treatment, PD rats displayed ethological changes, which resembled LID in human. The study of Immunoehemicalhistory study revealed that long - time use of levodopa reduced the expression of β - arrestinl. TCM could stop the decrease of β - arrestinl, of which TCM - medium group was （ 3.67±0.56 ） x 10^4, which is higher than that in PD group （ t = 6. 80, P 〈 0.01 ）. Western blot showed that compared to levodopa group which was （65.44 ± 6.68 ）% , the levels of β -arrestinl were in- creased to （73.62± 3.82） % and （72.56 ± 6.66 ） % in TCM - medium and TCM - high groups （ t = 3. 11, t = 3.70, P 〈 0. 05 ）. There was no difference between TCM - medium and TCM - high groups. Conclusions ： TCM can increase the ex- pression of β - arrestinl in rats, and reduce the occurrence of levodopa - induced dyskinesia.

关 键 词：帕金森病 左旋多巴 异动症 天芪平颤颗粒 β-arrestin1 

分 类 号：R741[医药卫生—神经病学与精神病学]