小剂量链脲佐菌素建立妊娠期糖尿病大鼠模型的研究

目的:探讨单次小剂量腹腔注射链脲佐菌素(STZ)诱导妊娠期糖尿病(GDM)大鼠模型的可行性,研究分析注射小剂量STZ前后孕鼠糖代谢等相关指标,并从形态学和功能学的角度评价模型。方法:将20只雌性Sprague-Dowlgy(SD)孕鼠随机分成模型组和对照组,每组各10只。模型组在孕1天单次腹腔注射STZ(25mg/kg),对照组用等量柠檬酸钠缓冲液同法处理。孕4天测定非空腹血糖,如血糖≥6.7mmol/L,则模型复制成功。孕18天进行口服葡萄糖试验(OGTT)及血清胰岛素测定,分别计算胰岛素抵抗指数(ISI)和胰岛素分泌能力指数(InsI),以评价胰岛素抵抗程度和胰岛素分泌能力。孕21天处死孕鼠,测定胎鼠体重和胎盘重量并取胰腺组织苏木精-伊红(H-E)染色、光镜检查。结果:模型组的胎鼠及胎盘重量大于对照组(P0.05),孕鼠非空腹血糖、OGTT各时段的血糖及胰岛素水平均高于对照组(P0.05)。模型组孕鼠的ISI高于对照组(P0.001),InsI低于对照组(P0.001)。模型组β细胞轻度损害,仅少数胰岛细胞呈空泡样变性。结论:单次小剂量腹腔注射STZ后成模孕鼠呈现了人类GDM的主要临床特征,是建立实验性GDM大鼠模型的理想方法之一。

A study on establishment of low-dose Streptozotocin-induced Gestational Diabetes in rats.

Objective：To establish the rat model of gestational diabetes （ GDM ） induced by administering Streptozotocin（ STZ） intraperitoneally with low dosage in single injection to investigate the proper method for duplicating reliable GDM model in pregnant rats. Method：Twenty virgin Sprague-Dowlgy（ SD） rats of comparable preweight were used for the experiments. The control group and the study group comprised 10 rats respectively. The study group was made diabetes by a single i. p injection of STZ （25mg/kg body wt） dissolved in 0. 1 M citrate buffer,PH 4. 2 on the first day of gestation,while the control group was injected with the buffer only at the same gestation age. Fasting and nonfasting blood glucose was determined on day 4,day 11 and day 18 of pregnancy. An oral glucose tolerance test（OGTT） was per-formed on the 18th day in each group to evaluate the degree of insulin resistance. On the 21st day the rats were sacrificed. The blood serums were determined for blood insulin and the pan-creas was removed for examination for morphological and ultra structural changes. Results：Non-fasting blood glucose in the study group was much higher than that in the control group. The level of blood glucose and insulin during OGTT in the study group was higher than that in the control group（P〈0. 05）. ISI in the study group was significantly higher（P〈0. 001）,but InsI was much lower than that in the control group（P〈0. 001）. The mild ？-cell damage in the study group was observed by means of the H-E staining. Conclusion：A single i. p injection of STZ may produce signs similar to those of GDM,such as higher levels in blood glucose and insulin, higher insulin resistance,lower insulin secretion and the mild ？-cell damage. Consequently,a single and low dose STZ could duplicate the rats model for GDM.