基因修饰的骨髓间充质干细胞移植治疗帕金森病的实验研究  

Intracerebral Transplantation of Nurr1 and TH Genes-modified Mesenchymal Stem Cells in Rat Model of Parkinson Disease

作　　者：刘晓艳[1] 康慧聪[1] 胡琦[1] 许峰[1] 李巷[1] 刘志广[1] 唐坤[1] 胡传琛[1] 朱遂强[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院神经内科,武汉430030

出　　处：《华中科技大学学报（医学版）》2011年第4期396-399,共4页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：国家自然科学基金资助项目(N30470603)

摘　　要：目的观察酪氨酸羟化酶(tyrosine hydroxylase,TH)和孤儿核受体相关因子1(nuclear receptor related factor1,Nurr1)基因修饰的骨髓间充质干细胞(MSCs)移植治疗帕金森病(PD)大鼠的有效性,验证并评价Nurr1对TH所起的调控作用,探寻TH在特定环境中适量表达的调控机制。方法将稳定转染TH、TH-Nurrl的和未经转染的MSCs分别移植至PD大鼠后运用旋转试验观测PD大鼠的行为学变化。移植后第9周应用免疫组织化学和Western blot检测移植治疗后TH的表达情况。结果基因修饰组PD大鼠行为学较MSCs组明显改善(P<0.05),且TH-Nurr1组动物行为改善和TH抗原阳性率均高于TH组(P<0.05)。结论基因修饰的MSCs移植后能高效稳定地表达TH,且双基因的协同表达将极大提高PD基因治疗的效果,从而为PD治疗的基因选择提供新的依据和思路。Objective To explore the potential use of mesenchymal stem cells（MSCs）modified by TH and Nurr1 gene in the treatment of Parkinson disease（PD）and the influence of nuclear receptor related factor 1（Nurr1）on the expression of tyrosine hydroxylase（TH）in vitro.Methods The recombinant retroviruses containing TH and Nurr1 genes were transferred into MSCs,respectively.The expression efficiency of TH in vitro was detected by immunocytochemistry and Western blot at 9th week after transplantation.Results MSCs modified by TH and Nurr1 genes could survive and express the exogenous TH gene stably in vitro.The TH positive cell number was significantly increased in TH-Nurr1 group（P〈0.05）.Conclusion The MSCs modified by TH gene can stably express TH.The MSCs in group of co-transfection intensify the expression of TH gene and may be developed as a useful therapy for PD.

关 键 词：骨髓间充质干细胞 孤儿核受体 酪氨酸羟化酶 帕金森病 

分 类 号：R742.5[医药卫生—神经病学与精神病学]