链脲佐菌素诱导长爪沙鼠Ⅰ型糖尿病模型的实验研究

A Mongolian Gerbil Model of Type 1 Diabetes Mellitus induced by Streptozotocin

目的探讨链脲佐菌素(STZ)诱导长爪沙鼠Ⅰ型糖尿病模型的可能性,并观察模型动物早期肾脏损害情况。方法雄性长爪沙鼠96只,随机分为正常对照组(NC组)、模型组1(DM1组)、模型组2(DM2组),DM1及DM2组沙鼠分别一次性腹腔注射100 mg/kg、200 mg/kg STZ,NC组注射等量柠檬酸盐缓冲溶液。注射STZ后1、2、4、6周末,分别监测沙鼠一般情况,血糖、胰岛素等血清学指标和尿液指标,并处死沙鼠进行胰腺和肾脏组织的病理学检查。结果注射STZ 24 h后,DM2组及DM1组部分沙鼠逐渐出现典型的"三多一少"症状,随着病程的发展,DM2组沙鼠持续高血糖,DM1组沙鼠血糖值与NC组差异有显著性(P<0.05),但有下降趋势;DM2组沙鼠胰岛素显著性降低(P<0.05),其他血清学指标及尿液指标均显著性升高(P<0.05),DM1组沙鼠各指标差异无显著性。DM2组沙鼠及DM1组少数沙鼠胰腺组织中可见胰岛β细胞减少、空泡样变性等变化,DM2组沙鼠肾脏组织中出现肾小球基质增多,毛细血管襻扩张等病变,DM1组沙鼠肾脏组织未见明显变化。结论 STZ 200 mg/kg可成功诱导长爪沙鼠Ⅰ型糖尿病模型,在病程早期沙鼠肾脏结构和功能已经发生改变。

Objective To explore the possibility of establishment of type 1 diabetic models in Mongolian gerbils induced by streptozotocin（STZ） and observe the early renal structural and functional changes of the gerbils.Methods Ninety-six Mongolian gerbils were divided randomly into normal control group（NC group） intraperitoneally（i.p.） injected with citric acid-citrate buffer solution,and diabetic model groups： DM1 and DM2 groups,i.p.injected with STZ at a dose of 100 and 200 mg /kg body weight,respectively.The gerbils were sacrificed at 1,2,4,6 weeks of the experiment,and autopsy was performed,serum index and urine index and pathological changes of the pancreas and kidney were examined.Results 24 h after STZ injection,the gerbils in DM2 group had distinct diabetic symptoms,showing consistent hyperglycemia,and compared with the normal control group,the blood glucose in DM1 group showed a statisticallysignificant difference（P 0.05）,the biochemical parameters except insulin in the DM2 group were significantly increased（P 0.05） with the progression of diabetes,while there was no statistical difference in the DM1 group.Pathological examination in the DM2 group revealed vacuolar degeneration,loss of β-cells in the pancreas,increase of the mesangial matrix and dilatation of glomerular capillaries in the kidney,while there were no distinct changes in the DM1 group.Conclusions Type 1 diabetic model in the Mongolian gerbils can be induced by STZ injection at a dose of 200 mg /kg.Structural and functional alterations of the kidney occurred in the diabetic gerbils in the early period.