单次大剂量对比多次小剂量STZ诱导昆明小鼠糖尿病肾病的研究

目的 研究单次大剂量注射与多次小剂量连续注射链脲佐菌素(STZ)诱导昆明小鼠糖尿病肾病的成模率,以得出最佳的建模方法.方法 26只昆明小鼠随机分为3组:阴性对照组6只(注射等量的柠檬酸盐缓冲液)、单次大剂量组10只(150 mg/kg单次腹腔注射)、多次小剂量组10只(40 mg/kg连续注射5d).末次注射后,每天记录饮水量,且于注射后第3、7、14、28天检测随机血糖,在注射STZ后4、10周各处死一半的小鼠,处死前分别测量小鼠体重和随机血糖,并记录小鼠成模后第2、4、10周24 h尿量;眼球取血测定血肌酐,血尿素氮;以及取肾脏组织作肾脏病理.结果 与单次大剂量组相比,多次小剂量组成模率高,死亡率低.单次大剂量组、多次小剂量组分别与阴性对照组相比,10周时24 h尿蛋白值均差异有统计学意义(P＜0.05).4周小鼠肾组织光镜无明显变化;10周出现肾小球肥大,系膜增生等.结论 多次小剂量注射STZ(40 mg/kg,连续注射5d)是合理的诱导糖尿病小鼠发生肾病的方法.

The study of single high-dose versus multiple low-dose of STZ in inducing diabetic nephropathy in Kunming mice

Objective To study the model of diabetic nephropathy in Kunming mice by single-dose high-dose injection and multiple doses of continuous injection of streptozotocin (STZ) to obtain the best modeling method.Methods Kunming mice (n =26) were randomly divided into 3 groups:mice in the negative control group (n--6) were injected with anequal volume of sodium citrate buffer intraperitoneally,mice in the single high-dose group (n =10)were injected with 150 mg/kg STZ only once,mice in the multiple low-dose group (n =10) were injected with 40 mg/kg STZ for 5 consecutive days.Then the water intake was recorded daily after the last injections.The blood glucose levels were examined in the 3th,7th,14th day and 4th,10th week.4 weeks and 10 weeks after injection,half of the mice were sacrificed respectively.The body weight and random blood glucose in mice were measured before death.The 24-hour urine volume were recorded in the 2nd,4-th,10th week.Serum creatinine(Scr),blood urea nitrogen(BUN) were determined by eyeball blood in the 4th,10th week,and the kidneys were taken for pathological examination.Results The multiple low-dose group displayed higher modeled rate and lower mortality than the single high-dose group.After 10 weeks,between negative control group and single high-dosegroup,the statistical significance existed in the 24-hour urine protein level of the mice,so did the negative control group and the multiple low-dose group.The renal pathological changes in the 4th week were not obvious,but they exhibited glomerular hypertrophy and mesangial proliferation in the 10th week.Conclusion The multiple low-dose STZ injection (40 mg/kg for 5 consecutive days) is a reasonable method for inducing mouse diabetic nephropathy.