【作者】 王磊；

【导师】 孙圣刚；

【作者基本信息】 华中科技大学 ， 神经病学， 2012， 博士

【摘要】 目的研究左旋多巴与脂质体诱发异动症大鼠模型的行为学特点和纹状体区多巴胺和环磷腺苷调节的磷酸化蛋白-32(DARPP-32)磷酸化状态的改变以及FosB/△FosB表达水平。方法对成功建立的6-羟多巴胺(6-OHDA)偏侧毁损致帕金森病(PD)大鼠模型分别予以壳聚糖修饰的左旋多巴脂质体／卡比多巴和左旋多巴／卡比多巴治疗4周,并在第1,4,8,12,16,20,24,27天观察其行为学；然后通过western-blotting检测异动症大鼠纹状体内DARPP-32蛋白Thr34位点磷酸化水平；通过免疫组化检测纹状体区FosB/△FosB的表达水平。结果在行为学观察中,异常不自主运动(AIM)评分在脂质体组与一般左旋多巴组皆随治疗时间延长而升高,但脂质体组评分明显低于一般左旋多巴组(P<0.05)；纹状体区DARPP-32的Thr34位点磷酸化水平在一般左旋多巴组毁损侧及脂质体组毁损侧较之对照组均有明显升高(P<0.05),但脂质体组毁损侧升高水平明显低于一般左旋多巴组毁损侧(P<0.05)；FosB/△FosB表达水平在一般左旋多巴组毁损侧及脂质体组毁损侧较之对照组均有明显升高(P<0.05),但脂质体组毁损侧升高水平明显低于般左旋多巴组毁损侧(P<0.05)。结论壳聚糖修饰的左旋多巴脂质体在减轻异动症表现的严重程度方面可能有效。更多还原

【Abstract】 Objective To study the effect to behavioral character and changes of phosphorylated Mr32000dopamine-and cyclic adenosine monophosphate-regulated phosphoprotein (DARPP-32) and FosB/AFosB in striatum of rat model of levodopa-induced dyskinesia (LID) by chitosan-coated levodopa liposomes.Methods Unilateral6-hydroxydopamine (6-OHDA) lesioned rat model of Parkinson disease (PD) was treated separatedly with chitosan-coated levodopa liposomes/carbidopa and levodopa/carbidopa once daily for4weeks and the behavior was observed on the1st,4th,8th,12th,16th,20th,24th and27th day. Then the animals were sacrificed, Phospho-Thr34DARPP-32level in striatum were measured by western blotting technique, and FosB/△FosB level in striatum were measured by immunohistochemical method.Results Scores of abnormal involuntary movement(AIM) decreased significantly in liposome group (P<0.05) compared with levodopa group (P<0.05). Levels of phospho-Thr34DARPP-32and FosB/△FosB in striatum increased significantly in levodopa group lesion side(P<0.05) and liposome group lesion side(P<0.05) compared with control group. However in liposome group lesion side, the expression of phospho-Thr34DARPP-32and FosB/△FosB in striatum decreased compared with levodopa group lesion side, and the differences between them were significant (P<0.05).Conclusion Chitosan-coated levodopa liposomes may be useful in the prevention and treatment of AIMs.更多还原