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母体乙醇暴露诱导的心脏纤维化与雄性仔鼠 TGF-β和 SIRT1/FOXO3a 信号改变有关:一项为期三个月的随访研究。

Maternal Ethanol Exposure-Induced Cardiac Fibrosis is Associated with Changes in TGF-β and SIRT1/FOXO3a Signaling in Male Rat Offspring: A Three-Month Follow-up Study.

机构信息

Nephrology and Kidney Transplant Research Center, Clinical Research Institute, Urmia University of Medical Sciences, Urmia, Iran.

Department of Physiology, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran.

出版信息

Cardiovasc Toxicol. 2022 Sep;22(9):858-865. doi: 10.1007/s12012-022-09761-7. Epub 2022 Jul 28.

Abstract

Ethanol exposure during pregnancy induces cardiac fibrosis in the fetal heart. However, the mechanisms by which consumption of ethanol induces fibrotic changes are not known. Pregnant rats were received ethanol 4.5 g/kg BW once per day from the 7th day of pregnancy (GD7) throughout lactation. Our findings demonstrated that, area of fibrosis increased in cardiac tissue in the pups on both postnatal day twenty one (PN21) and postnatal day ninety (PN90) after prenatal and early postnatal period ethanol treatment compared with the controls. It was accompanied by a decline in the expression of SIRT1 protein along with the elevation of FOXO3a and TGF-β protein expressions which were determined by western blot. Overall, our data reveal that prenatal alcohol usage increase in fibrotic regions in the pup hearts possibly by regulating TGF-β, FOXO3a and SIRT1 protein levels. These are potential therapeutic molecular targets that can be modulated to protect heart against maternal ethanol exposure.

摘要

孕期乙醇暴露会导致胎儿心脏纤维化。然而,目前尚不清楚乙醇摄入如何引起纤维化改变。怀孕的大鼠从妊娠第 7 天(GD7)开始每天接受 4.5g/kg BW 的乙醇,直至哺乳期。我们的研究结果表明,与对照组相比,在产前和早期产后乙醇处理后的仔鼠出生后第 21 天(PN21)和第 90 天(PN90),心脏组织中的纤维化面积增加。这伴随着 SIRT1 蛋白表达的下降,以及 FOXO3a 和 TGF-β 蛋白表达的升高,这些都是通过 Western blot 确定的。总的来说,我们的数据表明,产前酒精使用会增加仔鼠心脏纤维化区域,可能是通过调节 TGF-β、FOXO3a 和 SIRT1 蛋白水平。这些是潜在的治疗分子靶点,可以调节它们以保护心脏免受母体乙醇暴露的影响。

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