宫内高血糖环境及生后早期过度喂养对子代大鼠代谢的远期影响

目的 通过建立大鼠孕期高糖模型,观察出生后早期过度喂养对子代远期代谢的影响.方法 成年Wistar大鼠妊娠第5天,给予链脲霉素50 mg/kg腹腔内注射,建立高糖环境模型.将子代大鼠分为3组:宫内血糖环境正常组(CP组):仔鼠8只;宫内高血糖环境模型鼠出生仔鼠,且每只糖尿病母鼠哺乳喂养8只仔鼠(DP-1组);宫内高血糖环境,每只糖尿病母鼠哺乳期喂养4只仔鼠(DP-2组).观察出生后3～10周3组仔鼠体重变化,仔鼠10周龄时行口服葡萄糖耐量实验(OGTT),11周龄行高胰岛素一正葡萄糖钳夹实验,并采用酶联免疫吸附法测量胰岛素水平评价其胰岛功能.结果 DP-1和DP-2组仔鼠出生后3～10周的体重增长率分别为(6.68±1.70)%和(6.03±1.85)%,均显著高于CP组[(4.74±0.93)%,P<0.05].3组仔鼠10周龄OGTT结果差异均无统计学意义(P>0.05);DP-1组基础胰岛素水平[(0.76±0.37)μg/L]低于CP组及DP-2组[(1.13±0.25)μg/L和(1.06±0.14)μg/L,P<0.05];DP-1组平均葡萄糖输注速率高于DP-2组[(4.93±1.11)U/(kg·h)与(3.72±1.07)U/(kg·h),P<0.05].结论 宫内高血糖环境暴露下的子代大鼠出生后3～10周体重增长过快,出生后早期过度喂养会加速胰岛素敏感性的下降.

Long-term effect of maternal hyperglycemia and postnatal overfeeding on offsprings of rats

Objective To establish the animal model of gestational diabetes mellitus (GDM to observe the long-term effect of maternal hyperglycemia and postnatal overfeeding on the metabolism of offsprings. Methods Streptozotocin (STZ, 50 mg/kg) was administered to Wistar rats intraperitoneally on the 5th day of gestation to induce animal GDM model. Offsprings were allocated into 3 groups: Group CP (n=8) were exposed to normal maternal hyperglycemic environment, group DP-1 (n=8) exposed to intrauterine hyperglycemia and every 8 pups breast-fed by one GMD mother and group DP-2 exposed to intrauterine hyperglycemia and every 4 pups breast-fed by one GDM mother (n=8). Weight gain between 3-10 weeks were recorded, OGTT at 10 weeks and hyperinsulinemia-euglycemia clamp technique was performed, and plasma insulin level was measured by ELISA at 11 weeks. Results Offsprings in DP-1 and DP-2 group had greater weight gain than group CP at 3-10 weeks after birth [(6.68±1.70)% and (6.03±1.85)% vs (4. 74±0.93)%, P< 0. 05], but no difference was found among the three groups in OGTT results (P> 0. 05). The baseline plasma insulin level was lower in the DP-1 group than in the DP-2 and CP group [(0. 76± 0. 37)μg/L vs (1.13±0. 25)μg/L and (1.06±0. 14)μg/L](P<0. 05). GIR60-120 was higher in DP-1 Offsprings of Wistar rats, exposed to intrauterine hyperglycemia, experience excessive weight gain at 3-10 weeks after birth. Overfeeding in early life expedites the decrease of insulin sensitivity in these offspings.