两种化学药物联合脂肪乳灌胃快速诱导大鼠2型糖尿病的实验研究

Experimental study of two chemical drugs combined with fat emulsion gavage to rapidly induce type 2 diabetes mellitus in rats

目的探讨链脲佐菌素(STZ)以及四氧嘧啶在短期建立大鼠2型糖尿病的实验效果。方法将48只SD大鼠随机分为对照组、STZ组及四氧嘧啶组,对照组每日饮用水灌胃,STZ组和四氧嘧啶组动物使用脂肪乳灌胃,14天后,STZ组动物腹腔注射STZ 30 mg/kg,四氧嘧啶组动物按照第1日120 mg/kg、次日100 mg/kg剂量腹腔注射四氧嘧啶。注射后第2日晚禁食12 h后,进行口服糖耐量试验,于第3日晚禁食12 h后,麻醉取血检测相关生化指标,处死动物,取下肝脏、肾脏、胰腺,制作相关脏器病理切片。结果实验前,各组血尿酸(UA)、肌酐(CR)、尿素氮(BUN)、三酰甘油(TG)、胆固醇(TC)、血糖(GLU)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)检测结果比较,差异均无统计学意义(均P>0.05)。实验后STZ组及四氧嘧啶组动物UA、CR、BUN、TG、TC检测结果均高于对照组(均P<0.05);糖耐量试验各阶段血糖值均大于对照组(均P<0.05),且两实验组血糖在90 min达到高峰,之后呈下降趋势;肝脏病理均出现脂肪变性及空泡变性,肾脏均无明显病理改变,四氧嘧啶组动物胰导管扩张、腔内充满胰液,STZ组胰腺未观察到明显病理改变。结论 STZ及四氧嘧啶均可用于大鼠2型糖尿病模型的快速建立,STZ具有更良好的稳定性。

Objective To explore the experimental effects of streptozotocin(STZ) and alloxan in the establishment of rat type 2 diabetes in short-term. Methods Totally 48 SD rats were randomly divided into control group,STZ group and alloxan group. The control group received daily drinking water by gavage. STZ group and alloxan group were treated with fat milk by gavage. After 14 days,the animals in STZ group were intraperitoneally injected with STZ 30 mg/kg,and the animals in the alloxan group were intraperitoneally injected with alloxan according to the first day at a dose of 120 mg/kg and the next day at a dose of 100 mg/kg.Oral glucose tolerance test was performed after fasting for 12 hours on the second day after the injection. After fasting for 12 hours on the third day of the evening,the rats were anesthetized to collect blood and detect biochemical indicators,the animals were sacrificed,and the liver,kidney,and pancreas were removed to make pathological sections of the organs. Results Before the experiment,there were no statistically significant differences in the results of serum uric acid(UA),creatinine(CR),urea nitrogen(BUN),triglyceride(TG),cholesterol(TC),blood glucose(GLU),high density lipoprotein(HDL-C),low density lipoprotein(LDL-C)among different groups(all P>0.05). After the experiment,the results of UA,CR,BUN,TG and TC in STZ group and alloxan group were higher than those in the control group(all P<0.05),the blood glucose value in each stage of the glucose tolerance test was greater than that in the control group(all P<0.05),the blood glucose reached a peak at 90 min in both groups,and then showed a decreasing trend. Fatty degeneration and vacuolar degeneration were observed in the liver,and no significant pathological changes were observed in the kidney. The pancreatic ducts were dilated and the lumen was filled with pancreatic fluid in the alloxan group,while no significant pathological changes were observed in the pancreas in the STZ group. Conclusion Both STZ and alloxan can be used for the rapid establishment of a rat type 2 diabetes model,STZ has better stability.