恒河猴糖尿病模型肾脏相关血液、尿液指标的动态观察与分析

Dynamic Analysis of Biochemistry and Urinalysis of Streptozotocininduced Diabetes Mellitus in Rhesus Monkeys

目的动态观察小剂量多次注射链脲佐菌素(STZ)诱导糖尿病恒河猴动物模型早期肾脏指标的变化。方法健康恒河猴5只,小剂量(30 mg/kg)多次静脉注射链脲佐菌素(STZ),血糖稳定大于7.0 mmol/L后每个月采集肾脏相关血清生化指标和尿常规。连续观察13个月。结果 5只动物的平均血糖在10w左右达到稳定,造模3个月后血糖值达到8.31±2.31 mmol/L,此后持续平稳上升。总蛋白、球蛋白、甘油三酯持续上升,分别在给药10个月、9个月出现显著性差异(P<0.05)。白球蛋白比值下降,在给药11个月开始出现显著性差异(P<0.05)。糖化血清蛋白(GSP)6个月出现显著性差异(P<0.05),9个月出现极显著性差异(P<0.01)。血糖与TP、GLOB、UREA、CR、Mg2+、GSP呈高度正相关关系,与A/G呈高度负相关关系。结论发现了与人类早期糖尿病肾病相似的血清学、尿液变化,可作为相关疾病发病机制、药效学等研究的可靠模型。

Objective To make a reproducible diabetes mellitus model in macaques intravenous injection with low dose streptozotocin（STZ）.Methods we used STZ（30 mg/kg of body weight,intravenously,3 days） to five macaques.The dynamic changes of the kidney related biochemistry index and routine urinalysis were measured for 13 months after the glucose is stable.Results Animal＇s average glucose is table at 10 week（8.31±2.31 mmol/L）.Compared with the contents before injection,TP,GLOB,TG increased significantly at 10 and 9 months（P 0.05）while A/G reduced in plasma in macaques 11 months after streptozotocin injection（P 0.01）.GSP have significant difference at 6 months（P 0.05） and great significant difference at 9 months（P 0.01）.Significantly positive correlations were observed between Glu and TP,GLOB,UREA,CR,Mg2＋,GSP.Significantly negative correlations were observed between Glu and A/G.Concusion The present Diabetes Mellitus model in nonhuman primate mimics human early stage of DN and may be useful in assessing safety and efficacy of protective agents.