3种小鼠品系的四氧嘧啶糖尿病模型建立及初步评价

发布时间：2018-06-02 07:50

本文选题：药物活性分析 + 近交系　；参考：《药物分析杂志》2015年11期

【摘要】：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。
[Abstract]:Objective: to compare the effects of diabetic modeling and model evaluation in different strains of mice, and to provide a basis for the rational selection of experimental animals for drug activity analysis. Methods: the model rate and mortality rate were calculated by intraperitoneal injection of alloxan in the closed group (KM) and inbred strain BALB / cC57BL / 6J mice. According to the results of modeling experiment, only male km and BALB/c mice with similar mortality and model rate were selected to evaluate the effect of diabetic model. The survival rate, body weight, fasting blood glucose, glucose tolerance, serum insulin and C-peptide contents were measured by intragastric administration of metformin hydrochloride. Results the success rate of modeling was the highest in the strain of: the female and male were 60% and 65%, respectively, the lowest were C57BL / 6J, the female and male were 15% and 20%, respectively, and the male was 60 layers, but all the female mice died. The mortality of female mice in the same strain was higher than that of male mice. The mortality rates of female and male km mice were 40% and 20%, respectively. The mortality rates of BALB- / c mice were 100% and 25%, respectively, and those of C57BL / 6J mice were 80% and 65%, respectively. The hyperglycemia model group and metformin group showed the symptoms of multi-diet, multi-drink and wasting gradually, and the body weight increased slowly compared with the normal control group and the difference was significant. Since all the BALB/c mice died during the experimental period, the glucose tolerance, serum insulin and C-peptide levels in km mice were measured at the end of the experiment. The serum data were also consistent with the diabetic model index. The values of blood glucose dispersion coefficient of KMN BALB / c mice at 0 h were 0.17 and 0.20 ~ 72 h, respectively. The values of blood glucose dispersion coefficient were 0.32 and 0.12, respectively. Conclusion: compared with the success rate of modeling and the characteristics of the established model, male km mice are better than the other two strains and are more suitable as model animals, but the discrete values of fasting blood glucose values before and after modeling show that the individual differences of closed group km mice are obvious. The consistency of data is not as good as that of inbred mice, which suggests that the modeling of inbred mice has its advantages, but the modeling method needs to be further optimized.
【作者单位】：中国食品药品检定研究院实验动物资源研究所;中国食品药品检定研究院食品药品安全评价研究所;
【分类号】：R-332;R587.1

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