自发性糖尿病GK大鼠糖尿病周围神经病变模型的建立

The establishment of diabetic peripheral neuropathy model in spontaneous diabetic GK rats

目的通过高脂饲养GK大鼠建立一种符合人类糖尿病周围神经病变（DPN）发病特点，又操作简单的DPN大鼠模型。方法7~8周龄SPF级雄性自发性2型糖尿病GK大鼠30只，喂养高脂饲料造模。另取30只SPF级正常Wistar大鼠作为正常组，喂养普通饲料。每周监测动物血糖、体质量、饮水量、饲料量。分别于干预8周、12周、16周后检测血清糖化血红蛋白、坐骨神经传导速度，取对侧坐骨神经做HE染色，TUNEL染色计算细胞凋亡指数。结果随着造模时间延长，GK大鼠逐渐出现多饮、多食、生长迟缓等表现。与正常组相比，造模12周及16周的大鼠血糖、糖化血红蛋白升高（P<0.01），感觉神经传导速度降低（P<0.01），运动神经传导速度有一定下降趋势（12周P<0.05，16周P>0.05），坐骨神经病理形态及雪旺细胞凋亡情况均提示DPN的形成，并与正常大鼠形成鲜明对照（凋亡指数P<0.01）。结论长期高脂饲料喂养的GK大鼠是DPN研究的良好模型，12周是较为成熟且经济的造模时间。

Objective To establish a simple diabetic peripheral neuropathy (DPN) rat model with the high fat-fed in GK rats. Methods A total of 30 GK rats (7-8 weeks) were fed with high-fat diet to establish the DPN model. Thirty normal Wistar rats were fed with ordinary diet (control group). The blood-sugar value, body mass, water-intake and food-intake were monitored every week in two groups. The serum level of glycosylated hemoglobin, the right sciatic nerve conduction velocity were detected at 8, 12 and 16 weeks respectively. The left sciatic nerve was used for HE and TUNEL staining.Results The manifestations of polydipsia, polyphagia and growth retardation were gradually appeared in GK rats. After 12 and 16 weeks, the blood-sugar and glycosylated hemoglobin were significantly increased in GK rats compared with those of normal Wistar rats (P < 0.01). The sensory nerve conduction velocity decreased obviously (P < 0.01). And motor nerve conduction velocity showed a certain decline trend (12 week P < 0.05,16 week P > 0.05). The sciatic nerve pathological features and Schwann cell apoptosis suggested that the model of DPN was successfully established (apoptosis index, P < 0.01). Conclusion GK rats fed by high-fat diet are the satisfactory models of the DPN in experimental research. And 12-week is a suitable and economical time for molding.