GDNF基因治疗对帕金森病小鼠TH阳性神经元损害及胃肠功能障碍的影响  

Effect of GDNF gene therapy in treating tyrosine hydroxylase positive neuron damage and gastrointestinal dysfunction in Parkinson mice

作　　者：吴少璞[1] 祁亚伟[1] 李学[1] 杨红旗[1] 马建军[1] WU Shaopu ,QI Yawei ,LI Xue ,YANG Hongqi ,MA Jianjun(Department of Neurology, Henan Provincial People＇s Hospital, Zhengzhou , Henan 450002, China)

机构地区：[1]河南省人民医院神经内科,郑州450002

出　　处：《重庆医学》2018年第24期3129-3133,共5页Chongqing medicine

基　　金：河南省科技攻关计划项目(162102310283)

摘　　要：目的研究巨噬细胞介导的胶质细胞源性神经营养因子(GDNF)基因治疗对帕金森病小鼠临床症状,以及对黑质酪氨酸羟化酶(TH)阳性神经元损害和胃肠功能障碍的影响。方法 60只小鼠分为对照组、实验组和健康组。实验组小鼠接受表达GDNF的慢病毒骨髓干细胞转导,对照组和健康组小鼠注射生理盐水。移植后对照组和实验组通过MPTP建立帕金森模型,健康组注射生理盐水。比较3组小鼠建模后行为学变化、TH阳性(H+)多巴胺能神经神经元细胞免疫组织化学染色结果和神经元数目数目、体质量变化、胃排空率和肠推进率。结果 GDNF在移植后的小鼠中成功表达。实验组小鼠爬杆时间明显长于健康组并明显短于对照组(P<0.05),实验组小鼠转棒停留时间明显短于健康组并明显长于对照组(P<0.05)。对照组、实验组和健康组小鼠的(TH+)多巴胺能神经神经元数目分别为:(8 610.26±833.64)、(1 117.54±1 037.18)、(1 369.87±1 440.16)×10-4/μm3,差异有统计学意义(P<0.01);实验组小鼠黑质中的TH+多巴胺神经元纤维比对照组更密、颜色更深,比健康组更疏、颜色更浅。造模前后对照组和实验组小鼠体质量明显下降;实验组小鼠体质量、胃排空率、小肠推进率明显低于健康组且高于对照组(P<0.05)。结论 GDNF基因疗法能够明显改善帕金森病小鼠的运动协调能力,修复TH+神经元细胞损伤,改善胃肠道功能障碍。Objective To investigate the effect of macrophage-mediated glial-derived neurotrophic factor（GDNF）therapy on clinical symptoms,tyrosine hydroxylase（TH）positive neuron damage and gastrointestinal dysfunction in Parkinson mice.Methods Sixty mice were divided into the control group,experimental group and healthy group.The experimental group mice received the transduction of bone marrow stem cells expressing GDNF lentivirus,the control group and healthy group were injected with normal saline.After transplantation,the control group and experimental group built the Parkinson model by MPTP,while the healthy group was injected by normal saline.The behavior change,immunohistochemical staining results of substantia nigra tyrosine hydroxylase positive（H^＋）dopaminergic neuron and neurons number,body mass change,gastric emptying rate and intestinal propulsive rate after constructing the model were compared among3 groups.Results GDNF was expressed successfully in mice after transplantation.The pole-climbing time in the experimental group was significantly longer than that in the healthy group and significantly shorter than that in the control group（P〈0.05）;the stick-turning standing time in the experimental group was significantly shorter than that in the healthy group and significantly longer than that in the control group（P〈0.05）.The numbers of TH^＋dopaminergic neuron in the control group,experimental group and healthy group were（8 610.26±833.64）,（1 117.54±1 037.18）and（1 369.87±1 440.16）×10^-4/μm^3 separately,which showed statistically significant difference（P〈0.01）;the substantia nigra TH^＋dopaminergic neurofibrils in the experimental group were more dense and darker compared with the control group,and more scatter and lighter compared with the healthy group.The body mass before and after constructing the model in the experimental and control group was significantly decreased;the body mass,gastric emptying rate and intestinal propulsive rate in the experimental group were

关 键 词：帕金森病 基因 胶质细胞源性神经营养因子 黑质酪氨酸羟化酶阳性 胃肠功能障碍 

分 类 号：R741.05[医药卫生—神经病学与精神病学]