孕期高盐饮食对胎鼠心肌细胞周期的影响

Effect of prenatal high-salt exposure on cardiac cell cycle in the fetal rats

目的观察孕期给予高盐饮食后,胎鼠心肌细胞周期是否有改变及其与血管紧张素Ⅱ(AngⅡ)的关系。方法将SD大鼠随机分为正常组和高盐组,在孕3至21 d分别给予正常盐饮食和高盐饮食,孕21 d时检测母鼠和胎鼠的血钠浓度、血浆渗透压、血浆AngⅡ浓度以及胎鼠心脏组织中的AngⅡ含量,称量孕21 d胎鼠的心脏质量后,分离出心肌细胞,培养后检测细胞周期。结果与正常组相比,高盐组母鼠和胎鼠的血钠、血浆渗透压无明显改变(均P>0.05),母鼠和胎鼠血浆AngⅡ浓度明显降低,而胎鼠心脏局部AngⅡ明显增加(均P<0.05)。胎鼠心肌细胞G1期比例明显降低而S期比例明显增加,AngⅡ明显降低心肌细胞G1期比例并明显增加S期比例(均P<0.05),AngⅡ受体1型(AT1R)阻断剂可以阻断AngⅡ引起的细胞周期改变,而AngⅡ受体2型(AT2R)阻断剂对由AngⅡ引起的细胞周期改变无影响。结论孕期高盐饮食可能激活了胎鼠心脏局部AngⅡ,进而改变心肌细胞周期和影响胎鼠心脏发育,且AT1R介导了AngⅡ对心肌细胞周期的影响。

Abstract： Objective To determine the effect of high-salt diet during pregnancy on angiotensin-re- lated cardiac cell cycles. Methods Pregnant Sprague-Dawley rats were randomized to either normal-salt diet or high-salt diet during gestational day 3 -21. Blood samples from maternal and fetal rats were pre- pared for measuring sodium, osmolality, and the hormones. Fetal heart weight was measured. Cardiac ceils were cultured for analyzing cell cycle. Results There was no significantly difference of blood sodium concentrations and osmolality in both maternal and fetal rats between the control and high-salt group （all P 〉 0.05）. High-salt diet caused plasma Ang Ⅱ decreased in both the mothers and fetuses, and Ang Ⅱ in the fetal myocardium was significantly increased （ all P 〉 0.05 ）. G1 phase percentage was significantly decreased, whereas S phase percentage was increased in the heart ceils from the high salt group compared with those from the control group （ all P 〉 0.05 ）. Ang Ⅱ decreased G1 phase percentage and increased S phase percentage in the cardiac cells. Losartan, AT1R antagonist, reversed the changes of Ⅱ and S phases induced by Ang Ⅱ. PD123319, AT2R antagonist, did not block the changes induced by Ang Ⅱ in the cardiac ceils. Conclusion High-salt diet during pregnancy may activate the local Ang Ⅱ in fetal rats heart. The effect of cell cycles was mediated by AT~ R.