Abstract: The aim of this study was to investigate the optimal dose for establishing the canine type I diabetes model by combined injection of streptozotocin and alloxan. Eighteen healthy mixed-breed dogs aged 9-12 months with an average weight of (5.09±0.30) kg were selected. and randomly divided into 6 groups with 3 replicates per group and 1 per replicate. Group I(20 mg·kg^-1/40 mg·kg^-1), II(30 mg·kg^-1/50 mg·kg^-1)and III(40 mg·kg^-1/60 mg·kg^-1)were given single intravenous injection of streptozotocin and alloxan mixture, respectively; Group IV(10 mg·kg^-1/20 mg·kg^-1), V(15 mg·kg^-1/25 mg·kg^-1)and VI(20 mg·kg^-1/30 mg·kg^-1) were given twice intravenous injection of streptozotocin and alloxan mixture, respectively. The interval between the two injections was 24 h. The diabetes modeling effect was evaluated by the changes of blood glucose, glucose tolerance, blood physiological and biochemical, and pancreatic histomorphology. The results showed as follows:1) The fasting blood glucose in groups I and IV had been at a normal level, but in group II and III both exceeded 15 mmol·L^-1 for 7 consecutive days. Although there was an increase in group V and VI, they did not exceed 10 mmol·L^-1 during the experiment. 2) According to the results of the intravenous glucose tolerance test, the blood glucose in every group rose to its peak within 15 minutes, and then groups I and IV gradually decreased to the pre-injection level, group V decreased but did not reach the pre-injection level, while group II, III and VI continued to maintain high levels. 3) The blood routine indexes of each group were in a normal physiological range. The blood routine indexes of each group were in a normal physiological range. The alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), urea (UREA), creatinine (CREA) of group III were all above the normal physiological range. 4) According to the results of pancreatic histomorphology, the islet structure in group II and III was significantly destroyed. The above results indicate that a single intravenous injection containing 30 mg·kg^-1 streptozotocin and 50 mg·kg^-1 alloxan can effectively establish the canine type I diabetes model, and the blood glucose level can exceed 15 mmol·L^-1 for 7 d consecutively without serious hepatorenal toxicity.

Key words: alloxan, streptozotocin, canine, animal model, diabetes