Wu Na, Yang Xinxin, Song Lu, Wei Jianglei, Liu Zhenguo
Department of Neurology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, People's Republic of China.
Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.
Drug Des Devel Ther. 2013 Dec 10;7:1481-9. doi: 10.2147/DDDT.S48488. eCollection 2013.
Recent studies have shown that expression of G protein-coupled receptor kinase 6 (GRK6) and β-arrestin1 in the striatum is closely associated with hyperactive dopamine receptors in rats with levodopa-induced dyskinesia (LID). Our research group has shown that Tianqi antitremor granules have a significant effect on the motor complications of Parkinson's disease (PD). However, whether Tianqi antitremor granules have an effect on the behavioral manifestations and expression of GRK6 and β-arrestin1 in rats with LID is unknown.
Rats with PD received twice daily intraperitoneal injections of levodopa for 4 weeks to induce dyskinesia. Rats with LID were randomly divided into five groups: an LID-control group, an LID group, a levodopa plus Tianqi antitremor granules as traditional Chinese medicine (TCM)-low group, a levodopa plus TCM-medium group, and levodopa plus TCM-high group. Peak intensity of rotations was measured. GRK6 and β-arrestin1 expression in the striatum of the dyskinetic rats was observed by immunohistochemistry and Western blotting.
Pulsatile treatment with levodopa induced abnormal involuntary movements in rats with PD similar to LID in patients with PD. We found that repeated levodopa administration increased peak rotations in dyskinetic rats. However, peak rotations were decreased in rats given levodopa plus the different doses of Tianqi antitremor granules. In accordance with changed behavior, GRK6 and β-arrestin1 expression was decreased in rats with PD and was persistently low in rats with LID, but this decrease was prevented by coadministration of levodopa and Tianqi antitremor granules.
Tianqi antitremor granules ameliorated levodopa-induced dyskinetic behavior, reversed the decrease in GRK6 and β-arrestin1 expression, and acted as a useful adjunctive medicine for the treatment of LID.
近期研究表明,在左旋多巴诱导的异动症(LID)大鼠中,纹状体内G蛋白偶联受体激酶6(GRK6)和β-抑制蛋白1的表达与多巴胺受体活性亢进密切相关。本研究团队已表明,天麻止颤颗粒对帕金森病(PD)的运动并发症有显著疗效。然而,天麻止颤颗粒对LID大鼠的行为表现以及GRK6和β-抑制蛋白1的表达是否有影响尚不清楚。
对PD大鼠每日腹腔注射两次左旋多巴,持续4周以诱导异动症。将LID大鼠随机分为五组:LID对照组、LID组、左旋多巴加低剂量天麻止颤颗粒的中药低剂量组、左旋多巴加中剂量天麻止颤颗粒的中药中剂量组和左旋多巴加中剂量天麻止颤颗粒的中药高剂量组。测量旋转峰值强度。通过免疫组织化学和蛋白质印迹法观察异动症大鼠纹状体内GRK6和β-抑制蛋白1的表达。
左旋多巴脉冲式给药诱导PD大鼠出现与PD患者LID相似的异常不自主运动。我们发现,重复给予左旋多巴会增加异动症大鼠的旋转峰值。然而,给予左旋多巴加不同剂量天麻止颤颗粒的大鼠旋转峰值降低。与行为变化一致,PD大鼠中GRK6和β-抑制蛋白1的表达降低,且在LID大鼠中持续处于低水平,但左旋多巴与天麻止颤颗粒联合给药可防止这种降低。
天麻止颤颗粒改善了左旋多巴诱导的异动症行为,逆转了GRK6和β-抑制蛋白1表达的降低,可作为治疗LID的有效辅助药物。