3种小鼠品系的四氧嘧啶糖尿病模型建立及初步评价

目的:比较不同品系小鼠糖尿病建模及模型评价效果,为合理选择药物活性分析实验动物提供方法依据。方法:选择封闭群KM、近交系BALB/c、C57BL/6J 3种小鼠,腹腔注射四氧嘧啶建模,并计算成模率和死亡率。参照建模实验结果,仅选择死亡率及成模率较接近的雄性KM和BALB/c小鼠进行糖尿病模型效果评估实验。通过灌胃已知阳性药物盐酸二甲双胍,测定实验各组生存率、体重、空腹血糖值、葡萄糖耐量、血清中胰岛素及C肽含量等指标评价模型效果。结果:KM品系建模成功率最高,雌雄分别为60%和65%,C57BL/6J最低,雌雄分别为15%和20%,BALB/c雄性为60%,但雌性小鼠全部死亡。同一品系的雌性小鼠比雄性小鼠死亡率高,雌雄KM小鼠死亡率分别为40%和20%,BALB/c小鼠分别为100%和25%,C57BL/6J小鼠分别为80%和65%。高血糖模型组及二甲双胍组小鼠均逐渐表现出多食多饮消瘦的症状,体重与正常对照组相比增长慢且差异显著。因BALB/c小鼠高血糖模型组实验期内全部死亡,所以实验末期仅测定了KM小鼠糖耐量、血清中胰岛素和C肽含量,测定的血清学数据也均符合糖尿病小鼠模型指标。KM、BALB/c小鼠0 h的血糖值离散系数的数值分别为0.17和0.20;72 h的血糖值离散系数数值分别为0.32和0.12。结论:综合比较建模成功率及建成模型的特征,雄性KM小鼠优于其他2个品系,更适合作为建模动物;但建模前后空腹血糖值的离散数值表明封闭群KM小鼠个体差异明显,数据一致性不及近交系小鼠,提示采用近交系小鼠建模具有其优势,但建模方法还需进一步优化。

Objective:To compare the establishment and the characters of diabetic models among different mouse strains,to provide methodological measures for reasonable choice of experimental animals for analysis of pharmaceutical activity.Methods:The diabetic mouse models were established by i.p.administration of alloxan(ALX)to KM(closed colony strain),BALB/c(inbred strain)and C57BL/6J mice(inbred strain),and the incidence rate and mortality was calculated.With reference to the established experiment results,male KM and BALB/c mice which had comparable mortality and model establishment rate were selected for evaluation experiment of diabetic model.The diabetic models were given metformin i.g.for 28 d.Survival rate,body weight,fasting blood sugar,glucose tolerance,insulin and C-peptide levels in serum were determined.Results:The results indicated that KM strain had the highest model establishment rate of 60% and 65% for females and males,respectively.While C57BL/6J strain had the lowest model establishment rate of 15% and 20% for females and males,respectively.Male BALB/c model had the establishment rate of 60%and all female BALB/c mice died.Under the same condition,the death rate of female mice was higher than that of male mice for the same strain.Female and male death rate was 40% and 20% in KM strain,respectively,while 100% and 25% in BALB/c strain and 80% and 65% in C57BL/6J strain.The diabetic mice and the mice injected with metformin gradually exhibited different degree of polyphagia syndrome,polydipsia and emaciation,and their weights increased much slower compared to normal mice,with significant differences.The death rate of BALB/c strain in hyperglycemia model group was 100% during the experiment and this group failed to complete the experiment.Therefore,after drug administration for 28 days,glucose tolerance,serum insulin and c-peptide values were only examined in KM strain,and the serologic values met the diabetic model target.The dispersion degrees of fasting blood glucose level of KM stain and BALB/c strain after ALX injection was 0.17 and 0.20 at 0 h,respectively,while 0.32 and 0.12 at 72 h.Conclusion:According to the results of successful establishment rate and the characters of the established model,male KM strain was more suitable to establish experimental diabetic models.However,its dispersion degree of fasting blood glucose level showed the individual difference was significant for KM mice in closed colony whose numerical consistency was inferior to inbred strain,implying the inbred strain had advantages for modeling.However,modeling methods needed to be further optimized.