孕产期母鼠体内给予尼古丁对其子代肾脏RAS发育的影响

目的通过观察孕期母鼠体内给予尼古丁对其子代肾脏血管紧张素Ⅱ——Ⅰ型受体（AT1R）、Ⅱ型受体（AT2R）的基因及蛋白表达的影响,为研究胎儿肾素血管紧张素系统（RAS）发育及相关胎源性疾病提供理论根据。方法 SD孕鼠随机分为正常组和尼古丁组,分别给予相应处理,于出生14d、5个月处死新生鼠及子代鼠,称量体质量和肾脏质量,计算肾脏指数,测定肾组织AT1R和AT2R mRNA和蛋白表达。结果与正常组相比,尼古丁组新生鼠体质量、肾脏质量及成年子代鼠的肾脏质量及肾脏的AT2R mRNA和蛋白水平表达均明显减少（均P〈0.05）,AT1R基因、蛋白表达水平无明显差异（P〉0.05）,但AT1R/AT2R mRNA比值明显升高（P〈0.05）,而成年子代鼠的体质量无明显差异（P〉0.05）。结论孕产期母鼠体内给予尼古丁可致胎鼠出生低体质量,但对成年后体质量没有影响,表现出明显的出生＂追赶现象＂;孕产期母鼠体内给予尼古丁可影响子代肾脏正常生长及AT2R的表达,从而影响子代肾脏RAS发育及功能的发挥。

Effect of Prenatal and Postnatal Nicotine Exposure on Renal Development in Neonate and offsping Stage in the Rats

Objective To determine the effect of maternal administration of nicotine on the development of the kidney in rats by examining the expression of renal angiotensin Ⅱ receptors（AT1R、AT2R） at mRNA and protein levels during postnatal development,and provide experiment evidence for fetal kidney programming and fetal origin-diseases.Methods SD pregnant rats were individed into two groups randomly,the diffrent treatment were given.Kidneys were removed and collected at ages of 14-day-old,5-month-old,AT1R,AT2R mRNA and protein abundance in both males and females at two developmental ages were examined.Results Unlike that in the control group,in the maternal exposed nicotine fetal body weight and kidney weight were dcreased ciganificantly,and kidney weight,renal AT2R mRNA and protein abundance notably reduced in 5-month offspings both in male and female（P〈0. 05）.AT1R mRNA and protein abundance of 5-month offspring both in male and female had on significant change compared with that in the the control group（P〉0.05）.However,the renal AT1R /AT2R ratio was significantly increased（P〈0. 05）.Conclusion Maternal administration of nicotine can reduce fetal body weight and show visible ＂grow-up＂effect.The results demonstrate that the development of renal angiotensin II receptor can maintain in changed following exposure to perinatal nicotine,and such change in the kidney can be long-term in postnatal life.