中文摘要：

目的 研究妊娠不同时期缺氧对成年雄性子代大鼠心脏局部血管紧张素转化酶-血管紧张素Ⅱ-血管紧张素Ⅱ1型（ACE-AngⅡ-AT1）受体轴的影响。方法 将SD孕鼠随机分为妊娠早期（G1，妊娠第3天）开始缺氧组、中期（G2，妊娠第9天）开始缺氧组、后期（G3，妊娠第15天）开始缺氧组和空白对照组（G0），每组各6只。缺氧组每日置于氧气浓度为10%±1%的低压氧舱3小时，直至自然分娩。各组雄性子代大鼠于3月龄及5月龄时酶联免疫吸附测定（ELISA）检测心脏局部AngⅡ,逆转录PCR检测心脏AT1、 AT2、胶原Ⅰ和胶原Ⅲ mRNA，Western blot检测心脏ACE、AT1、 AT2、磷酸化细胞外信号调节激酶1/2（phosphorylated extracellular signal-regulated kinase 1/2，pERK1/2）蛋白表达情况。结果 妊娠早、中期缺氧引起3月龄雄性子代大鼠心脏局部ACE、AngⅡ的升高（均P〈0.05），以及3月龄和5月龄子代大鼠心脏AT1受体mRNA及蛋白表达增加（均P〈0.05），并使5月龄子代大鼠心脏AT2受体mRNA及蛋白表达减少（P〈0.05），而妊娠晚期缺氧仅会改变5月龄子代大鼠心脏AT1和AT2受体表达（均P〈0.05）。妊娠中期缺氧引起3月龄和5月龄雄性子代大鼠心脏局部pERK1/2、胶原ⅠmRNA和胶原ⅢmRNA表达增加（均P〈0.05），妊娠早期缺氧仅引起5月龄子代大鼠心脏局部pERK1/2、胶原ⅠmRNA和胶原ⅢmRNA表达增加（均P〈0.05），而妊娠晚期缺氧则无影响（均P〉0.05）。结论 妊娠期缺氧会引起成年雄性子代大鼠心脏局部ACE-AngⅡ-AT1轴活化，以妊娠早期或中期开始的缺氧对该轴影响最明显，并促进了下游ERK的磷酸化和心脏胶原沉积。

英文摘要：

Aim To evaluate whether the timing of maternal hypoxia during pregnancy influenced cardiac angiotensin converting enzyme （ACE） - angiotensinⅡ （AngⅡ） - angiotensin type 1 receptor （AT1） in the adult offspring. Methods Pregnant rats were randomly assigned to maternal hypoxia group starting from early period of pregnancy （G1,day 3 to 21 of pregnancy）,group starting from middle period of pregnancy （G2,day 9 to 21 of pregnancy）,group starting from late period of pregnancy （G3, day 15 to 21 of pregnancy）,or control group. There were 6 rats for each group. Rats of maternal hypoxia groups were subjected to hypoxia for 3 hours in low pressure cabin with an oxygen concentration of 10%±1%. The level of cardiac AngⅡ was detected by Enzyme linked immunosorbent assay （ELISA） in the adult male offspring at the age of 3 months and 5 months. The mRNA expression levels of cardiac AT1,AT2,collagenⅠand collagen Ⅲ were measured by reverse transcription PCR. The protein levels of cardiac ACE,AT1,AT2 and phosphorylated extracellular signal-regulated kinase 1/2 （pERK1/2） were also detected. Results Maternal hypoxia from day 3 to 21,or from day 9 to 21 of pregnancy induced increased expression levels of cardiac ACE and AngⅡ in male offspring at the age of 3 months （all P〈0.05）. They also induced increased mRNA expression levels and protein levels of cardiac AT1 in male offspring at the age of 3 months and 5 months （all P〈0.05）. And they lead to decreased mRNA expression level and protein level of cardiac AT2 in male offspring at the age of 5 months （all P〈0.05）. But maternal hypoxia from day 15 to 21 affected the expression of AT1 and AT2 only in male offspring at the age of 5 months （all P〈0.05）. Maternal hypoxia from day 9 to 21 lead to increased protein levels of cardiac pERK1/2 and increased mRNA expression levels collagenⅠand collagen Ⅲ（all P〈0.05）. Maternal hypoxia from day 3 to 21 increased the expression of cardiac pERK1/2,collagenⅠmRNA and collagen