高脂饲料联合链脲佐菌素诱导妊娠期糖尿病大鼠模型的优化方案

Optimization of gestational diabetes mellitus induced by high-fat diet combined with streptozotocin

目的:探讨高脂饲料喂养联合链脲佐菌素(streptozotocin,STZ)建立妊娠期糖尿病大鼠模型的优化方案,明确STZ的最佳剂量。方法:将6周龄的SPF级大鼠适应性喂养1周之后给予高脂饲料喂养8周,按照雌鼠与雄鼠2∶1的比例进行合笼,次日阴道涂片镜检发现精子记为孕第1天。将所得孕鼠随机分为对照组及STZ不同剂量(15,25,35,45 mg/kg)组,分别一次性腹腔注射同等剂量枸橼酸缓冲液(0.1 mol/L,p H=4.2)及STZ,观察体重、空腹血糖以及成模率、死亡率、仔鼠情况,HE染色观察孕鼠的胰腺、肝脏及脂肪组织的变化。结果:25 mg/kg组成模率(62.5%)最高,死亡率(12.5%)最低;注射STZ后25、35、45 mg/kg组血糖均明显升高,且25 mg/kg组较平稳。结论:SPF级6周龄Wistar大鼠高脂饲养8周联合孕第1天注射25 mg/kg STZ为建立稳定的妊娠期糖尿病大鼠模型的可靠方式。

Objective： To explore the reliable method of establishing the rat model of gestational diabetes with high fat feed combined with streptozotocin（STZ）, and to establish the best dose of stable STZ rat model of gestational diabetes mellitus. Methods： The 6week old SPF rats were fed a highfat diet for 8 weeks after one week of adaptive feeding.According to the ratio of two females to one male, the next day vaginal smear was examined, if the sperm was found D1 day pregnant was recorded. The pregnant rats were randomly divided into control group and STZ groups （15,25,35,45 mg/kg）.They were given intraperitoneal injection of the same volume of citric acid buffer （0.1 mol/L, pH=4.2） or STZ 15, 25, 35, 45 mg/kg respectively.Body weight, fasting blood glucose and the rate of moled formation, mortality, offspring were measured or observed. In addition the pancreas, liver and adipose tissue in pregnant rats were assessed by HE staining. Results： The moleding rate of 25 mg/kg group was 62.5%, which was the highest,and the death rate of 12.5% is the lowest.After injection of STZ, blood glucose level of 25,35 and 45 mg/kg groups increased significantly, and the blood level of 25 mg/kg group was more stable. Conclusion： SPF grade 6week old Wistar rats were fed highfat diet for 8 weeks and STZ at the dosage of 25 mg/kg was injected on the first day of gestation, which was a reliable way to establish a stable model of gestational diabetes mellitus in rats.