链脲佐菌素和四氧嘧啶联合注射建立犬I型糖尿病模型

Combined Induction of Streptozotocin and Alloxan to Establish the Canine Type I Diabetes Model

旨在探索链脲佐菌素和四氧嘧啶联合注射建立犬I型糖尿病模型的最佳剂量。本试验选取18只9~12月龄、平均体重为(5.09±0.30)kg的健康中华田园犬,随机分为6组(每组3个重复,每个重复1只)。按链脲佐菌素和四氧嘧啶不同剂量混合分组,其中Ⅰ组(20 mg·kg^(-1)/40 mg·kg^(-1))、Ⅱ组(30 mg·kg^(-1)/50 mg·kg^(-1))和Ⅲ组(40 mg·kg^(-1)/60 mg·kg^(-1))进行单次静脉注射;Ⅳ组(10 mg·kg^(-1)/20 mg·kg^(-1))、Ⅴ组(15 mg·kg^(-1)/25 mg·kg^(-1))和Ⅵ组(20 mg·kg^(-1)/30 mg·kg^(-1))进行两次静脉注射,两次注射间隔为24 h。通过注射后血糖、葡萄糖耐量、血液生理生化和胰腺组织形态学变化来评价各组建模效果。结果显示:1)Ⅰ组和Ⅳ组的空腹血糖始终处于正常水平,Ⅱ组和Ⅲ组连续7 d超过15 mmol·L^(-1),Ⅴ组和Ⅵ组虽有上升,但试验期间均未超过10 mmol·L^(-1);2)葡萄糖耐量试验显示,各组血糖均在15 min升高至峰值,之后Ⅰ组和Ⅳ组逐渐下降到注射前水平,Ⅴ组血糖虽下降但未达到注射前水平,Ⅱ组、Ⅲ组和Ⅵ组持续保持高血糖水平;3)各组血常规指标均在正常生理范围内,Ⅲ组的丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、碱性磷酸酶(ALP)、尿素(UREA)和肌酐(CREA)均超过正常生理范围;4)胰腺组织形态学显示,Ⅱ组和Ⅲ组的胰岛结构被明显破坏。综上所述,对犬使用30 mg·kg^(-1)+50 mg·kg^(-1)的链脲佐菌素和四氧嘧啶联合单次静脉注射,血糖值连续7 d大于15 mmol·L^(-1)且未造成严重的肝肾毒性,可有效建立I型糖尿病模型。

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.