邻苯二甲酸酯宫内暴露对子代小鼠致肥作用的研究

In utero exposure to monoethyl-hexyl-phthalate induces obesity of offspring in mouse model

目的:研究围产期宫内暴露邻苯二甲酸酯(MEHP)对子代小鼠肥胖的程序化作用。方法:不同剂量MEHP(0.05、0.25、0.5mg/kg体重)灌胃处理孕鼠做为低中高剂量组,等体积橄榄油灌胃处理的孕鼠做为对照组。处理周期为孕鼠妊娠第12天直至新生鼠出生后第7天。每周监测仔鼠体重直至第8周,并检测8周龄仔鼠的肝重、脂肪垫质量、血脂和血糖水平。结果:3组剂量MEHP宫内暴露均引起新生仔鼠体重增加(P<0.001);成年后(8周龄)雌性仔鼠体重接近对照组,而低剂量组成年雄性仔鼠体重明显高于对照组(P<0.01),附睾和肾周脂肪垫质量明显增加(P<0.001和P<0.01),血清总胆固醇、甘油三酯和血糖水平明显上升(P<0.01、P<0.05、P<0.001)。中高剂量对成年雄性仔鼠的体重、体脂组成、血脂和血糖水平无明显影响。结论:MEHP可以增加子代雄鼠肥胖发生风险,它可能作为一种潜在的化学诱导因子诱发肥胖及相关疾病发生。

Objective： To examine whether perinatal exposure of mouse to monoethyl - hexyl - phthalate （MEHP） causes the development of obesity in offspring. Methods： Pregnant mice were dosed by gavage with vehicle （olive oil） or MEHP（0.05, 0.25 or 0.5 mg/kg） from day 12 of gestation until day 7 of lactation. The body weight of offsprings was measured every week from the birth until 8 weeks of age. The liver weight, fat mass, and serum lipids and glucose levels were measured in off- springs at the 8th week after birth. Results ： In utero exposure to MEHP （0.05, 0.25 or 0.5 mg/kg b. w. ） increased the body weight of offsprings at birth （P 〈0.001 ）. The body weight of female offsprings in MEHP group was not significantly dif- ferent from that of controls at 8 weeks of age, while the exposure to low dose MEHP increased the body weight （ P 〈 0.01 ） , epididymal and perirenal fat mass （P 〈0. 001 and P 〈0.01, respectively） in male offsprings at 8 weeks of age. In addition, serum cholesterol, triglyceride and glucose levels were also significantly elevated （ P 〈 0.01, P 〈 0.05 and P 〈 0. 001, re- spectively） in the MEHP exposed male offsprings. The exposure to medium or high dose MEHP had no effect on body weight, body fat, serum lipids and glucose levels in male offsprings. Conclusion： MEHP may increase the incidence of obesity and may act as a potential chemical stressor for obesity and obesity - related disorders.