壳聚糖修饰左旋多巴纳米脂质体对异动症大鼠行为学及多巴胺和环磷腺苷调节的磷酸化蛋白32磷酸化水平的影响  

Effects of chitosan-coated levodopa nanoliposomes on behaviour and levels of phosphorylated Mr 32 000 dopamine-and cyclic adenosine monophosphate-regulated phosphoprotein in rats with dyskinesia

作　　者：王磊[1] 严丹[1] 肖海兵[1] 孙圣刚[1] 徐岩[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院神经科,湖北省武汉市430022

出　　处：《中国组织工程研究》2012年第12期2125-2128,共4页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金资助项目(30700881)~~

摘　　要：背景:左旋多巴是目前治疗帕金森病最主要的药物,但是长期应用后大多数患者会出现异动症等难以控制的运动并发症。目的:观察左旋多巴与纳米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蛋白磷酸化状态的改变。方法:建立6-羟多巴胺偏侧毁损致帕金森病大鼠模型,25只成功造模大鼠随机分为3组,帕金森病生理盐水组(n=5),一般左旋多巴组(n=10),壳聚糖修饰的左旋多巴纳米脂质体组(n=10),分别予以生理盐水、卡比多巴和左旋多巴、壳聚糖修饰的左旋多巴纳米脂质体治疗4周。结果与结论:在行为学观察中,异常不自主运动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);纹状体区多巴胺和环磷腺苷调节的磷酸化蛋白32的Thr-34位点磷酸化水平在一般左旋多巴组及脂质体组较对照组均明显升高(P<0.05),但脂质体组升高水平明显低于一般左旋多巴组(P<0.05)。提示壳聚糖修饰的左旋多巴纳米脂质体在防治帕金森病异动症方面可能有效。BACKGROUND：Levodopa is the main drug for treatment of Parkinson＇s disease,but most patients suffer from levodopa-induced dyskinesias after a long-term administration.OBJECTIVE：To study the effect of chitosan-coated levodopa nanoliposomes on behavioral characters and levels of phosphorylated Mr 32 000 dopamine-and cyclic adenosine monophosphate-regulated phosphoprotein（DARPP-32） in the striatum of rat models of levodopa-induced dyskinesia.METHODS：Unilateral 6-hydroxydopamine lesioned rat models of Parkinson＇s disease were established in 25 rats and divided into three groups treated separately with chitosan-coated levodopa nanoliposomes（liposome group,n=10）,carbidopa and levodopa（levodopa group,n=10）,and normal saline（control group,n=5） once daily for 4 weeks.RESULTS AND CONCLUSION：Levels of phospho-Thr34 DARPP-32 in the striatum and scores of abnormal involuntary movement increased significantly in the levodopa group（P 0.05） and liposome group（P 0.05） compared with the control group.However in the liposome group,the expression of phospho-Thr34 DARPP-32 in the striatum decreased compared with the levodopa group,scores of abnormal involuntary movement decreased also,and the differences between them were significant（P 0.05）.Chitosan-coated levodopa nanoliposomes may be useful in the prevention and treatment of dyskinesias to parkinsonian patients.

关 键 词：左旋多巴纳米脂质体 壳聚糖 持续性多巴胺刺激 帕金森病 异动症 多巴胺和环磷腺苷调节的磷酸化蛋白32 

分 类 号：R318[医药卫生—生物医学工程]