目的探讨稳定、可靠与妊娠期胰岛素抵抗相似的小鼠模型建立方法。方法将60只SPF级5周龄KM小鼠随机分为高脂饮食组和普食组,高脂饮食组高脂饲料喂养4周后,按雌雄1∶1合笼,在雌鼠阴道看到阴道栓定位妊娠第一天。妊娠成功后,按30 mg/kg间隔24 h腹腔注射,共注射3次,对照组注射等量的柠檬酸缓冲液(0.1 mol/L,p H=4.2)。于造模成功后的第3、7、14及19天记录小鼠的随机血糖,体重,以及24 h的饮水量和摄食量。ELISA检测血清中INS、ADP、LEP和CRP因子的浓度。结果孕鼠在造模成功后出现明显饮水量、摄食量、尿量增多症状,饮水量、摄食量与对照组相比有显著差异(P11.1 mmol/L,明显高于对照组。GDM组INS(1.50±0.25)Mu/L,ADP(0.65±0.13)μg/L,LEP(1.60±0.12)μg/L,CRP(37.54±4.70)μg/L,与对照组相比差异极显著(P〈0.01)。产后,小鼠血糖恢复到正常水平。结论高脂饮食结合小剂量STZ多次诱导的方法能够建立的GDM模型且符合人类妊娠期糖尿病病理性胰岛素抵抗的特征。
Objective To explore a gestational insulin resistance mice model establishing method,which is steady,reliable and similar to human being. Method Female KM mice at 5 weeks were randomly divided into high fat diet group( n = 30) and normal diet group( n = 30). High fat diet group was exposed to high diet for 4 weeks,and then male and female were mated( n ∶ n = 1 ∶ 1) Then the pregnancy mice were intraperitoneal injected with 30 mg / kg / d STZ during the first 3 days,the control group was injected with equal dosage of citrate buffer solution( 0. 1 mol / L,p H = 4. 2)for 3 days. Their blood glucose,body weight,the amount of food intake and water intake were recorded at 3,7,14 and 19 d of the GDM model respectively. The serum INS,ADP,LEP,CRP were measured by ELISA. Results We successfully made the GDM mice model,and the pregnant mice showed significant signs of polyuria,polydipsia,hyperphagia and weight loss compared to the control model( P 〈 0. 01). The blood glucose of GDM mice 〉11. 1mmol / L,the serum cytokines( INS( 1. 50 ± 0. 25) Mu / L,ADP( 0. 65 ± 0. 13) μg / L,LEP( 1. 60 ± 0. 12) μg / L,CRP( 37. 54 ± 4. 70) μg /L) of GDM mice were significant difference compared to the control model( P 〈 0. 01). Postpartum,the GDM mice blood glucose returned to the normal level. Conclusion Gestational diabetes mellitus mice model can be successfully developed by high fat diet with low dose STZ and three times induce,which preferable mimics the characteristic of gestational pathologic insulin resistance in human beings.