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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 detect the effect of hepatic insulin gene therapy on diabetic neuropathy. Methods: The diabetic model was established by penile injection of streptozotocin. The mice were randomly divided into normal control group, diabetic group and diabetic gene therapy group. The gene therapy group received hepatic insulin gene therapy and the remaining two groups received blank virus control expressing only green fluorescent protein. The mice in each group were randomly divided into three groups: random blood glucose, body mass, methylene blue, emptying rate, total length of intestinal tract, absolute and relative distance of methylene blue in intestinal tract, electric stimulation of colon transmural wall and colonic count. Results: The mouse model of diabetic neuropathy was successfully established. Specifically manifested as: 8 weeks sustained hyperglycemia, prolonged total length of the gut, methylene blue relative shortening the forward distance, loss of diastolic capacity of the colon smooth muscle and decreased colon inhibitory nucleus. The diabetic gene therapy group of mice can effectively prevent or improve the above abnormal indicators, thereby preventing the occurrence of enteric neuropathy. Conclusion: Hepatic insulin gene therapy can effectively prevent intestinal neuropathy in streptozotocin-induced diabetic mice.