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  

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

作　　者：姚亚兰 王金霞 阚春明[1] 吴永贵[1] 王坤[1] 

机构地区：[1]安徽医科大学第一附属医院肾脏内科,合肥230022

出　　处：《安徽医科大学学报》2017年第12期1786-1790,共5页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:81374034)

摘　　要：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5 d)。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5 d)是合理的诱导糖尿病小鼠发生肾病的方法。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 3 th,7 th,14 th day and 4 th,10 th 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 2 nd,4 th,10 th week. Serum creatinine（ Scr）,blood urea nitrogen（ BUN） were determined by eyeball blood in the 4 th,10 th 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 4 th week were not obvious,but they exhibited glomerular hypertrophy and mesangial proliferation in the 10 th week. Conclusion The multiple low-dose STZ injection（40 mg/kg for 5 consecutive days） is a reasonable method for inducing mouse diabetic nephropathy.

关 键 词：链脲佐菌素 糖尿病肾病 不同剂量 昆明小鼠 

分 类 号：R587.1[医药卫生—内分泌]