肝脏胰岛素基因治疗对链脲霉素糖尿病小鼠肠神经病变的疗效

摘要

目的:检测肝脏胰岛素基因治疗对糖尿病肠神经病变的疗效.方法:经阴茎静脉注射链脲霉素建立糖尿病模型,并随机将小鼠分为正常对照组,糖尿病组和糖尿病基因治疗组.基因治疗组接受肝脏胰岛素基因治疗,其余2组仅接受表达绿色荧光蛋白的空白病毒对照.观察各组小鼠随机血糖、体质量、亚甲基蓝排空率、肠道总长度、亚甲基蓝肠道绝对和相对前进距离,结肠透壁电刺激反应以及结肠神经核染色计数.结果:成功建立糖尿病肠神经病变小鼠模型.具体表现为:8周持续高血糖状态,肠道总长度的延长,亚甲基蓝相对前进距离缩短,结肠平滑肌舒张能力受损以及结肠抑制性神经核减少.而糖尿病基因治疗组小鼠可有效预防或改善上述异常指标,从而阻止肠神经病变的发生.结论:肝脏胰岛素基因治疗可有效预防链脲霉素糖尿病小鼠肠神经病变.%Objective To evaluate the effect of hepatic insulin gene therapy on diabetic enteric neuropathy.Methods Mice were randomly allocated into 3 groups: a normal control group, a diabetic group, and a diabetic gene therapy group.Diabetes were induced by penial vein injection of streptozocin (STZ).The gene therapy group received hepatic insulin gene therapy while the other 2 groups only received an empty virus expressing green fluorescent protein.Random blood glucose,body weight growth, gastric emptying, total bowel length, absolute and relative bowel transit, electric field stimulation of colon smooth muscle, colon nuclei staining and counting were measured.Results We successully established a mouse model of diabetic enteric neuropathy which manifests as:8 weeks of continuous hyperglycemia,increased total bowel length, decreased relative bowel transit,impaired colon smooth muscle relaxation and loss of inhibitory neurons in colon.Through gene therapy, the above indexes were normalized or ameliorated, suggesting hepatic insulin gene therapy is capable of preventing diabetic enteric neuropathy.Conclusion Hepatic insulin gene therapy can prevent STZ induced diabetic enteric neuropathy.