微移植内侧神经节隆起细胞治疗亨廷顿病大鼠模型的效果  

Micro-transplantation of ganglionic eminence cells reduces Huntington-associated phenotypes in rats

作　　者：刘杰 刘驰 皮水平 陈绪刚 黄前樟 黎成[3] 朱明欣[3] 蒋伟[3] 

机构地区：[1]湖北省大冶市人民医院神经外科,大冶435100 [2]湖北省大冶市人民医院神经内科,大冶435100 [3]华中科技大学同济医学院附属同济医院神经外科

出　　处：《中华行为医学与脑科学杂志》2015年第8期689-693,共5页Chinese Journal of Behavioral Medicine and Brain Science

基　　金：基金项目：湖北省自然科学基金项目（2012FFC00301）;国家自然科学基金青年基金项目（81100946）

摘　　要：目的 探究采用神经微移植技术和传统移植技术将内侧神经节隆起细胞移植至亨廷顿病大鼠模型的疗效异同.方法 75只雌性成年SD大鼠,采用随机数字表法分为四组：对照组（ctrl,n=15）、假移植组（ST,n=20）、传统移植组（TT,n=20）和微移植组（MT,n=20）,应用神经微移植技术（针头直径为50μm）和传统的移植技术（针头直径为470 μm）将神经节隆起细胞或磷酸缓冲盐溶液移植入单侧奎宁酸（Quinic acid,QA）损毁的大鼠纹状内,奎宁酸诱导损伤后及移植后第2,4,6,8,10,12周进行阿扑吗啡诱导的旋转试验和步移试验,移植12周后分析神经元核抗原（neuron specific nuclear protein,NeuN）、多巴胺、cAMP调节的磷蛋白（dopamine and adenosine 3′5′-monophosphate-regulated phospho-protein,Mr 32 kD,DARPP-32）、胶质纤维酸性蛋白（glial fibrillary acidic protein,GFAP）的表达.结果 在移植12周后,与TT组相比,MT组大鼠步移实验表现较好,TT组和MT组DARPP-32阳性细胞数目分别为（9 690±651）个和（13 194±976）个,差异具有统计学意义（P=0.020）,TT组和MT组单侧移植物周围GFAP阳性细胞数目分别为（11 352±1 421）个和（6 558±694）个,差异具有统计学意义（P=0.002）,TT组和MT组移植后存活率分别为55％和85％,差异具有统计学意义（P=0.012）.结论 微移植技术能提高内侧神经节隆起细胞移植治疗HD大鼠模型的效果,这些发现为HD的细胞移植治疗奠定了基础.Objective To compare the therapeutic effects of microtransplantation method and traditional transplantation method for transplanting ganglionic eminence cell into HD rats.Methods Seventy-five adult female Sprague-Dawley rats were randomly divided into four groups,control group （ctrl;n=15）,sham transplantation group （ST;n=20）,traditional transplantation group （TT;n=20）,and microtransplantation group （MT;n =20）.Ganglionic eminence cells or phosphate-buffered saline were transplanted into unilateral striatum of quinic acid lesion rats with micro-transplantation instruments （with an outer diameter of 50 μm） or traditional transplantation instruments （with an outer diameter of 470 μm）.Apomorphine-induced rotation test and adjusting step test were assessed after QA-induced lesion and 2,4,6,8,10 and 12 weeks after transplantation.The expression of neuronal nuclei （NeuN）,dopamine,cAMP-regulated phosphoprotein of molecular weight 32 kDa （DARPP-32）,and glial fibrillary acidic protein （GFAP） were analyzed at 12 weeks after transplantation.Results Compared with traditional transplantation group,microtransplantation group performed well in stepping test.DARPP-32 positives cell in MT group （13 194±976） had a significantly larger number compared with TT group（9 690±651） （P=0.020）.The TT group（11 352± 1 421） had a significantly larger number of GFAP-positive cells compared with MT groups （6 558 ± ±694） （P=0.002）.The survival rate of the MT group（85%） during the 12 weeks after transplantation was significantly higher than that of the TT groups（55%） （P=0.012）.Conclusion Micro-transplantation approach can minimize the trauma associated with transplantation and also provide accurate targets in the host brain.It may be an alternative transplantation strategy for Huntington＇s disease.

关 键 词：内侧神经节隆起细胞 神经微移植 亨廷顿病大鼠模型 细胞存活率 功能修复 

分 类 号：R741[医药卫生—神经病学与精神病学] R-332[医药卫生—临床医学]