Primate models of diabetes induced by streptozotocin / 中国组织工程研究

ABSTRACT

BACKGROUND: It is of great importance in improving the clinical effect of human islet allograft to study and design models of such large animals as pigs or primates preclinically.OBJECTIVE: To evaluate the effect of different doses of streptozotocin (STZ) on inducing diabetes type Ⅰ models of nonhuman primates.DESIGN, TIME AND SETTING: A contrast observational animal experiment was performed in the Cell Transplantation and Gene Therapy Center, the Third Xiangya Hospital of Central South University from October 2007 to December 2008. MATERIALS A total of 21 adult male rhesus monkeys were divided into a 125 mg/kg STZ group (n =5), a 75 mg/kg STZ group (n=5) and a 50 mg/kg STZ group (n=11).METHODS: STZ weighed with regard to body mass of animals was prepared into 25 g/L STZ solution with buffer that was prepared in advance. After being filtered and degermed, the new-prepared STZ of 125 mg/kg, 75 mg/kg and 50 mg/kg were administered by intravenous injection into the experimental monkeys respectively, which took 1-5 minutes.MAIN OUTCOME MEASURES: Liver and renal function, glucose metabolism and histomorphological changes of animals during 1-16 weeks following administration.RESULTS: In 125 mg/kg STZ group, two rhesus monkeys died, in 8 hours following STZ administration, of serious hypoglycemia caused by severely damaged pancreas β cells; All rhesus monkeys in this group had got significantly increased liver transaminase, serum creatinine and urea nitrogen at week 1 following STZ administration, which reached a peak during 2-4 weeks; One rhesus monkey in this group showed severe shortage of endogenous trypsin and hyperglycemia irreversible by exogenous insulin following STZ administration, and finally died at day 13 following STZ administration due to the glucose metabolic disorder, ketoacidosis, liver and renal failure; The other two survivors in this group kept high level of liver transaminase,urea nitrogen and serum creatinine throughout the observation period. In 75 mg/kg STZ group, rhesus monkeys presented significantly increased liver transaminase, serum creatinine and urea nitrogen at week 1-2 following STZ administration; After 4 weeks following administration, their liver and renal function presented with abnormality of different degrees; One rhesus monkey in this group had got injured renal function, decreased power of resistance, eyelid edema, general dropsy and irreversible infected rump after injection of STZ, and finally died at the end of week 5 following administration; Another rhesus in this group presented with irreversible continuous hyperglycemia, inappetence and significantly decreased weight, and finally died ofsystemic failure at week 9 following administration. In the 50 mg/kg STZ group, renal function of monkeys were slightly affected, with a transient mild rise which return to the normal level by the end of week 4 following administration; Only 3 animals in this group appeared eyelid edema during 1-4 weeks following administration which disappeared afterwards.CONCLUSION: STZ of 50 mg/kg is possibly the optimal dose for inducing diabetes models in most rhesus monkeys.