左旋多巴诱导帕金森病异动症与纹状体DARPP-32磷酸化的关系  

The relationship between levodopa-induced dyskinesia and phosphorylation of DARPP-32 in the striatum in experimental Parkinson disease

作　　者：宋璐[1] 马雅萍[1] 刘振国[1] 巴茂文[1] 卞雷斯[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,200092

出　　处：《中国神经免疫学和神经病学杂志》2011年第1期1-4,共4页Chinese Journal of Neuroimmunology and Neurology

基　　金：上海市科委纳米技术专项基金资助项目(No.0952nm03700);上海市科委基础研究重点项目(No.09JC1411000);上海市教委科研创新重点项目(No.10ZZ72);上海市白玉兰科技人才基金资助项目(No.1009B097)

摘　　要：目的观察帕金森病(PD)异动症(LID)大鼠模型纹状体区多巴胺和环磷腺苷调节的磷酸化蛋白-32(DARPP-32)蛋白Thr75位点磷酸化表达数量及表达位点的改变。方法给予PD大鼠模型左旋多巴治疗21d,评估大鼠行为学变化;采用免疫荧光和Western blot检测大鼠纹状体区DARPP-32蛋白Thr75位点磷酸化表达数量和表达部位的改变情况。结果 PD大鼠长期使用左旋多巴出现类似于人类LID行为学表现。免疫荧光结果显示PD组和LID组大鼠损伤侧DARPP-32(Thr75)的表达多位于强啡肽阳性神经元。Western blot结果显示PD组大鼠损伤侧DARPP-32(Thr75)表达为(159.90±7.22)%,与假手术组比较升高(P<0.05);LID组大鼠损伤侧纹状体DARPP-32(Thr75)的表达为(52.60±4.45)%,与假手术组和PD组比较降低(P<0.05)。结论纹状体黑质投射神经元内DARPP-32蛋白Thr75位点磷酸化表达的改变可能参与了LID的发病。Objective To investigate the changes of DARPP-32 phosphorylation in the striatum in experimental Parkinson disease （PD） rats with levodopa-induced dyskinesia （LID）. Methods The PD rats were intraperitoneally treated with levodopa for 21 days. Immunoflourescent stain and Western blot were used to observe the changes of DARPP-32 （Thr75） phosphorylation in the striatum. Results After levodopa treatment, PD rats displayed ethological changes, which resembled LID in human. The study of immunoflourescent study revealed that the phosphorylation of DARPP-32 at Thr75 site were mostly located in dynorphin positive neurons in the lesion side in PD and LID rats. Western blot revealed that phosphorylated DARPP-32 （Thr75） in LID rats [（52.60±4. 45）%] was less than in PD rats [（159.90±7.22）%] and in sham-operated rats （P〈0.05）. Conclusions These results suggested that the changes of DARPP-32 （Thr75） phosphorylation status in the striatalnigral neurons could play an important role in the pathogenesis of LID.

关 键 词：帕金森病 左旋多巴 DARPP-32 强啡肽 磷酸化 

分 类 号：R742.5[医药卫生—神经病学与精神病学]