DARPP-32磷酸化与止颤汤改善大鼠帕金森病运动并发症的研究

摘要

目的 观察纹状体多巴胺和环磷腺苷调节的磷酸化蛋白-32(DARPP-32)(Thr34)磷酸化与止颤汤对大鼠帕金森病运动并发症的影响.方法 采用6-羟基多巴胺(6-OHDA)注射于大鼠脑部黑质造成帕金森病(PD)模型,进一步予以左旋多巴/苄丝肼腹腔注射制作异动症(LID)模型.实验设立正常组,LID模型组,LID西药组及小剂量中药组、中剂量中药组、大剂量中药组,并采用免疫组化法观察各组大鼠DARPP-32(Thr34)磷酸化的表达情况.结果 免疫组化显示,假手术组DARPP-32(Thr34)磷酸化表达明显低于模型组(P<0.01).中药小剂量组、中剂量组、大剂量组DARPP-32磷酸化表达与西药组表达比较,差异有统计学意义(P<0.05);中剂量组磷酸化与小剂量组比较,差异有统计学意义(P<0.05).结论 止颤汤可有效降低纹状体DARPP-32(Thr34)磷酸化的表达,可能是止颤汤治疗异动症的机制.%Objective To study the effects of Zhichan decoction (ZCD) on the phosphorylation of the dopamine and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32) at Thr34 in striatum of Parkinsonian rats with abnormal involuntary movements (AIM).Methods Six unilatera1 hydroxydopamine-lesioned rat,the mode1 of Parkinson disease (PD),were treated with levodopa/benserazide in order to establish the rats models with levodopa-induced dyskinesia (LID).LID rats were randomly divided into 5 groups: LID model groups treated with saline,levodopa group and ZCD low doses group,ZCD medium doses group and ZCD high doses group,respectively.Five rats with sham-operation were served as controls.Rats were then sacrificed,and immunohistochemica1 techniques was used to measure the expression of phosphorylated DARPP-32 at Thr34 in striatum.Results Immunohistochemistry showed that the expression of phosphorylated DARPP-32 at Thr34 in striatum in LID model group was higher than that in control group (P<0.01).The expressions of phosphorylated DARPP-32 at Thr34 in striatum in ZCD groups were lower than that in levodopa group (P<0.01).The expression of phosphorylated DARPP-32 at Thr34 in striatum in ZCD medium doses group was lower than that in ZCD low doses group (P<0.05).Conclusion ZCD can down-regulate the expression of phosphorylated DARPP-32 at Thr34 in striatum in Parkinsonian rats with LID.