单次大剂量对比多次小剂量STZ诱导C57BL/6J小鼠糖尿病肾病模型的研究  

Single high-dose versus multiple low-dose streptozotocin for inducing diabetic nephropathy in C57BL/6J mice

作　　者：冷昌龙 皮明山 龚晓康 LENG Changlong;PI Mingshan;GONG Xiaokang(Wuhan Institute of Biomedical Sciences,Jianghan University,Wuhan 430000,China)

机构地区：[1]江汉大学武汉生物医学研究院,武汉430000

出　　处：《中国比较医学杂志》2021年第9期113-118,共6页Chinese Journal of Comparative Medicine

摘　　要：目的对比研究不同剂量链脲佐菌素(streptozotocin,STZ)联合高糖高脂饮食诱导C57BL/6J小鼠糖尿病肾病模型的稳定性。方法 48只雄性C57BL/6J小鼠随机分为:对照组(注射等体积柠檬酸缓冲液,12只),单次大剂量(150 mg/kg STZ,单次腹腔注射联合高脂高糖,18只),多次小剂量剂量(50 mg/kg STZ,连续注射4 d联合高脂高糖,18只)。检测两种造模方法在空腹血糖(fasting blood glucose,FBG)、饮水量、血脂、24 h尿蛋白、肾功能及肾病理等方面的改变。结果注射STZ后,单次大剂量组小鼠体重缓慢增加,而多次小剂量组小鼠体重出现负增长;单次大剂量小鼠FBG、饮水量在注射STZ 4周后达到峰值,24 h尿蛋白在注射STZ 6周后达到峰值,随后逐渐降低;多次小剂量组FBG、24 h尿蛋白及饮水量一直稳定上升并维持在较高水平;实验结束时多次小剂量组小鼠FBG、24 h尿蛋白、血清甘油三酯(triglyceride,TG)、总胆固醇(total cholesterol,TC)、低密度脂蛋白(low density lipoprotein,LDL)、血清肌酐(serum creatinine,Scr)、血清尿素氮(blood urea nitrogen,BUN)、肾脏指数(kidney index,KI)及肾小球还原糖水平均显著高于单次大剂量组(P<0.05),且肾病理改变更为明显。结论多次小剂量注射STZ联合高糖高脂饮食建立小鼠糖尿病肾病成模率高、死亡率低、稳定性好,具有人类糖尿病肾病相似的发病过程和病理特征,是理想的糖尿病肾病造模方法。Objective To explore the optimal method of producing a streptozotocin-induced diabetic nephropathy C57BL/6 mice model by investigating a molded rate of single high-dose and multiple low-dose streptozotocin injections.Methods Male C57BL/6 J mice( n = 48) were randomly divided into three groups: the normal group and two diabetic nephropathy groups. Mice in one model group( the single high-dose group) were intraperitoneally administered 150 mg/kg streptozotocin after having a high fat/high sucrose diet. The other model group( the multiple low-dose group) was intraperitoneally administered 50 mg/kg streptozotocin for 4 consecutive days after having a high fat/high sucrose diet. The fasting blood glucose levels,body weight,water intake,24 h urine protein,renal function and renal pathological changes of the three groups were measured. Results The body weight of the single high-dose group increased stably after streptozotocin injection,while the body weight of the multiple low-dose group decreased by inches after streptozotocin injection. Moreover,the fasting blood glucose levels,water intake and 24 h urine protein increased stably in the multiple low-dose group from week 2 to week 10. The levels of fasting blood glucose,24 h urine protein,total cholesterol,triglycerides,low density lipoprotein,serum creatinine,blood urea nitrogen and kidney/body weight ratio were significantly higher in the multiple low-dose group than in the single high-dose group( P < 0. 05) and the change in pathology was apparent. Conclusions The multiple low-dose streptozotocin injection protocol is a reasonable method for inducing mouse diabetic nephropathy.

关 键 词：糖尿病肾病 链脲佐菌素 高糖高脂饮食 C57BL/6J小鼠 

分 类 号：R-33[医药卫生]