C57BL/Ksj db/＋小鼠作为妊娠期糖尿病模型的可行性

Feasibility of C57BL/Ksj db/＋ mice used as the model of gestational diabetes mellitus

目的 了解C57BL/Ksj db/＋小鼠妊娠期糖代谢特点,为将其作为妊娠期糖尿病（gestational diabetes mellitus,GDM）的动物模型提供依据. 方法 随机选取C57BL/Ksj db/＋（杂合组）与野生型雌鼠（对照组）各10只,分别与同龄野生型C57BL/Ksj雄鼠配对.以合笼前第3天、妊娠第6、11、17天和产后第6天分别为妊娠前期、妊娠早期、妊娠中期、妊娠晚期和产后期.分析2组雌鼠妊娠前期、妊娠不同时期及产后糖耐量、空腹胰岛素水平.为动态监测2组雌鼠妊娠期血清瘦素水平,以妊娠第6、11、14、17、20（临产前）天为妊娠期5个时间点,分析2组雌鼠妊娠不同时期的瘦素水平.数据采用单因素方差分析中的Tukey法进行分析. 结果 （1）杂合组孕鼠较对照组孕鼠糖耐量明显降低,空腹胰岛素水平随妊娠期进展明显升高[妊娠第6、11、17天分别为（8.6±0.6）mU/L与（7.5±1.1）mU/L、（9.8±0.6） mU/L与（8.5±1.1）mU/L和（10.4±0.8）mU/L与（9.9±0.5）mU/L,t值分别为1.859、4.056和3.078,P值分别为0.085、0.000和0.000],产后与妊娠前期差异无统计学意义.（2）杂合组孕鼠血清瘦素水平明显高于非妊娠期[妊娠前期、妊娠第6、11、14、17、20天,血清瘦素水平分别为（911.0±238.8） ng/L、（1 342.2±132.3） ng/L、（1 821.9±238.2） ng/L、（1 816.3±142.3） ng/L、（1 752.4±126.6） ng/L、（1 926.4±61.6） ng/L;t值分别为3.887、8.210、8.161、7.585和9.153,P值分别为0.005、0.000、0.000、0.000和0.000],但妊娠中期以后瘦素水平未呈现随妊娠期进展明显升高的趋势. 结论 C57BL/Ksj db/＋雌鼠妊娠期空腹和餐后血糖的改变、胰岛素及瘦素水平的变化与GDM患者相似,即空腹胰岛素水平随妊娠期进展明显升高,产后恢复正常,糖耐量逐渐降低,瘦素水平明显高于非妊娠期,与孕周无明显相关性,可将其作为GDM的动物模型.

Objective To identify the glycometabolism features ofC57BL/Ksj db/＋ mice at gestational period and provide the evidence for the mice used as the animal model of gestational diabetes mellitus （GDM）.Methods Ten C57BL/Ksj db/＋ female mice and ten wild female mice were randomly selected and mated with wild male mice respectively.Day 3 before mating,days 6,11 and 17 of pregnancy,and day 6 after delivery represented pre pregnancy,early-pregnancy,mid-pregnancy,late-pregnancy and post-pregnancy periods,respectively.The levels of glucose tolerance and fasting insulin of female mice were compared at progestation,different gestational periods and puerperium between the two groups.Days 6,11,14,17 and 20 （before labor） of pregnancy served as five time-points of pregnancy,leptin levels of female mice of the two groups were dynamically monitored during pregnancy,and analyzed at different gestational ages.The data were analyzed by Tukey test of one-way ANOVA.Results （1） Compared with the normal pregnant mice,the levels of glucose tolerance of C57BL/Ksj db/＋ female mice were significantly decreased,while the levels of fasting insulin were dramatically increased with the progression of pregnancy [day 6 of pregnancy,（8.6 ± 0.6） mU/L vs （7.5 ±1.1） mU/L; day 11 of pregnancy,（9.8±0.6） mU/L vs （8.5± 1.1） mU/L; day 17 of pregnancy,（10.4±0.8） mU/L vs （9.9±0.5） mU/L; t=1.859,4.056 and 3.078,P=0.085,0.000 and 0.000] and recovered to the pre-pregnancy level after delivery.（2） The level of leptin in serum of C57BL/Ksj db/＋ pregnant mice was significantly higher than that at non-pregnant period [pre-pregnancy and days 6,11,14,17 and 20 of pregnancy：（911.0±238.8） ng/L,（1 342.2± 132.3） ng/L,（1 821.9±238.2） ng/L,（1 816.3± 142.3） ng/L,（1 752.4± 126.6） ng/L,and （1 926.4±61.6） ng/L,respectively; t=3.887,8.210,8.161,7.585 and 9.153,P=0.005,0.000,0.000,0.000 and 0.000],but showed no apparent change with the gestational ages after mid-gestation.Conclusion Changes of glycometabolism and the levels of leptin and insulin of C57BL/Ksj db/＋ pregnant mice during pregnancy are similar to those of GDM patients,the levels of fasting insulin are dramatically increased with the progression of pregnancy,and return to normal after delivery,the level of leptin is higher than that at non-pregnant period,but is not correlated with the gestational ages.C57BL/Ksj db/＋ pregnant mice can be used as the animal model of GDM.