宫内缺氧对子代大鼠血浆及肝脏RAS的影响

Effects of prenatal hypoxia on renin-angiotensin system in plasma and liver of offspring rats

目的研究宫内缺氧(PH)对子代大鼠血液循环系统和肝脏局部肾素-血管紧张素系统(RAS)的影响,以探讨PH导致子代脂肪肝易感性增加的可能机制,寻找药物干预靶点。方法利用饲养舱饲养建立妊娠期宫内缺氧大鼠模型,分别称量孕21 d胎鼠、成年子代大鼠(5月龄)、成年子代大鼠缺氧应激(7 d)后的体重、肝重,并计算肝重指数,检测大鼠血浆及肝脏中AngⅠ、AngⅡ和ACE的含量。结果与正常组相比,PH组胎鼠体重、肝脏重量及肝重指数明显下降,成年后各组这些差别消失;但给予7 d缺氧应激后,PH成年子代大鼠肝重及肝重指数较正常成年子代明显升高。胎鼠两组间和成年子代大鼠两组间血浆及肝脏中AngⅠ和ACE含量均无显著差异;PH成年子代肝脏中AngⅡ含量明显高于正常子代。经过7 d缺氧应激后,大鼠肝脏中的AngⅠ含量和血浆及肝脏中AngⅡ含量均较未缺氧应激组明显升高;宫内缺氧成年子代大鼠肝脏中ACE含量和血浆及肝脏中AngⅡ含量升高幅度均明显大于正常成年子代组。结论PH可引起子代胎儿期及成年后肝脏局部RAS组份含量增高,使得其子代成年后RAS在缺氧刺激后更易被激活,这可能是PH导致子代脂肪肝易感性增加的机制之一。

Aim To study the effects of prenatal hy-poxia on the risk of fatty liver disease to search the drug targets .Methods Intrauterine hypoxia rats model was established .The bodies and livers of fetal rats of 21 days, and adult offspring rats of 5 months with and without anoxic treatment were all weighed .The liver index was calculated and the concentrations of renin-angiotensin system components in circulation system and livers of offspring rats were measured .Results The weight of the bodies , livers and index of liver weight to body weight （ liver index ） were significantly decreased in the PH group compared with the normal group.These differences disappeared in adulthood . However, the liver index of adult offsprings in the PH group after hypoxia stress for 7 days was significantly increased compared with that of adult offsprings in nor-mal group.There were no significant differences in the concentrations of AngⅠ, AngⅡ and ACE in plasma＆nbsp;and livers between the two groups of fetal rats and the two groups of adult offspring rats separately .The con-centrations of AngⅡ in the livers of adult rats in PH group were significantly higher than those in normal group.The concentrations of AngⅠ in livers and the concentrations of AngⅡ in plasma and livers in the group treated with hypoxia stress for 7 days were signif-icantly higher than those without hypoxia stress .The concentrations of ACE in livers and the concentrations of AngⅡ in plasma and livers in PH adult offsprings were significantly higher than those of normal adult off-springs .Conclusion PH can induce the increase of RAS content in the livers of fetus and adult rats , RAS is more likely to be activated after hypoxia stimulation in the following adulthood .PH is a potential mecha-nism that mediates offspring susceptibility of fatty liver .