G蛋白偶联受体激酶6参与天芪平颤颗粒预防帕金森病异动症的发生

目的：研究天芪平颤颗粒对左旋多巴诱发的异动症大鼠行为学及G蛋白偶联受体激酶6（Gprotein—coupled receptor kinase6，GRK6）表达的影响。方法：通过6-羟基多巴（6-hydroxydopa，6-OHDA）立体定向注射至大鼠前脑内侧束的方法成功建立帕金森病（Parkinson disease，PD）模型。25只模型大鼠随机分为5组，每组各5只。PD组：腹腔注射0．2％维生素C溶液；左旋多巴组：腹腔注射左旋多巴甲酯和苄丝肼；小、中、大剂量天芪平颤颗粒组：在给予左旋多巴甲酯和苄丝肼基础上分别加用相应剂量的天芪平颤颗粒。另设假手术组（n=5）为对照。连续给药29d后，评估不同剂量天芪平颤颗粒对PD模型大鼠行为学的影响，并用免疫组织化学法和蛋白质印迹法检测大鼠纹状体区GRK6蛋白的表达情况。结果：左旋多巴等长期使用后，PD模型大鼠出现异常不自主运动（abnormal involuntarv movement，AIM），且AIM评分随治疗时间的延长逐渐增加；损伤侧纹状体区GRK6蛋白表达减少。天芪平颤颗粒能改善PD模型大鼠的AIM评分，增加GRK6蛋白的表达。免疫组织化学法结果显示，高、中剂量天芪平颤颗粒组的GRK6蛋白的表达较左旋多巴组增加（P〈0．05）；蛋白质印迹法结果显示，中剂量天芪平颤颗粒组的GRK6蛋白的表达较左旋多巴组增加（P〈0．01）。结论：天芪平颤颗粒可能通过增加纹状体区GRK6的表达，改善PD模型大鼠的AIM评分，减少PD大鼠异动症的发生。

Effects of Chinese herbal medicine Tianqi Pingchan Granule on G proteincoupled receptor kinase 6 involved in the prevention of levodopainduced dyskinesia in rats with Parkinson disease

OBJECTIVE： To investigate the effects of Tianqi Pingchan （TQPC） Granule, a compound traditional Chinese herbal medicine with antitremor activity, on levodopa-induced dyskinesia and the expression of G proteincoupled receptor kinase 6 （GRK6） in rats with Parkinson disease （PD）. METHODS： The hemi-Parkinsonian rat model was established by sterotaxically injecting 6-hydroxydopa （6- OHDA） to the right medial forebrain bundle. Rats with PD were randomly divided into 5 groups with 5 in each. PD group was intraperitoneally injected with vitamin C; levodopa group was intraperitoneally injected with levodopa and benserazide; low-, medium- and high-dose TQPC Granule groups were intraperitoneally injected with levodopa and benserazide and treated with different dosages of TQPC Granule by gavage for 29 d. Another 5 rats were served as control with sham-operation. The behaviors of rats were observed and classified with abnormal involuntary movement （AIM） score. The expression of GRK6 in the striate of rats was detected by immunohistochemical method and Western blotting. RESULTS： AIM score was increased and the expression of GRK6 protein in lesion side was decreased after the long-tern treatment with levodopa and benserazide in rats. The AIM scores of rats with PD were decreased after TGPC Granule treatment. Immunohistochemical results showed that the number of GRK6-positive cells in medium- and high-dose TQPC Granule groups was increased as compared to that in the levodopa group （P〈0.05）. The expression level of GRK6 protein was increased in medium-dose TQPC Granule group when compared with the levodopa group （P〈0.01）, which was observed by Western blotting. CONCLUSION： TGPC Granule can increase the expression of GRK6, inhibit the increase of AIM, and reduce the incidence of levodopa-induced dyskinesia in rats with PD.