Department of the Prenatal Diagnosis Center, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fujian Key Laboratory for Prenatal Diagnosis and Birth Defect, Fuzhou, China.
Department of Obstetrics and Gynecology, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Daoshan Road 18, Gulou District, Fuzhou, 350005, Fujian, China.
BMC Cardiovasc Disord. 2020 Mar 17;20(1):139. doi: 10.1186/s12872-020-01418-z.
BACKGROUND: The incidence of CHD is the highest among birth defects and is increasing year to year. CHD seriously harms the health of infants and young children and presents a large economic burden to families and society. The pathogenesis of CHD and preventive measures are the focus of current research. Our research aimed to explore the intervention effect of folic acid on heart abnormalities resulting from sodium arsenic (NaAsO) exposure during the periconception period. METHODS: Sixty 35-day-old female SD rats were randomly divided into 5 groups with 12 rats in each group. Group A was the control group. The rats were given distilled water and ordinary chow. The rats in group B were given distilled water containing 75 mg/L NaAsO and ordinary chow. The rats in groups C, D, and E were given distilled water containing 75 mg/L NaAsO and chow containing 0.53 mg/kg, 5.3 mg/kg, and 10.6 mg/kg folic acid, respectively. The general condition of the embryos and the histopathology of the embryonic hearts were examined. The acetylation levels of histone H3K9 in heart tissues and the expression levels of Mef2C (which is related to heart development) were observed. RESULTS: The embryo weight and placental weight of groups B-E were significantly lower than those of group A (P < 0.05). The heart malformation rate of the fetal rats in groups B-E was significantly higher than that of the fetal rats in group A (P < 0.05). We found that the level of H3K9 acetylation in fetal rat cardiomyocytes in groups B-E was significantly higher than that in group A (P < 0.05) and that the level of H3K9 acetylation in groups C-E was lower than that in group B (P < 0.05). The mRNA level of Mef2C in fetal rat cardiomyocytes in group B-E was significantly higher than that in group A (P < 0.05), and the mRNA level of Mef2C in groups C-E was significantly lower than that in group B (P < 0.05). CONCLUSION: Supplementation with folic acid during the periconception period can interfere with the toxic effects of arsenic on the heart. The mechanism may be that lowering the acetylation levels of histone H3K9 in heart tissues leads to decreased expression levels of Mef2C, which may play a protective role in heart development in fetal rats.
背景：先天性心脏病（CHD）是出生缺陷中发病率最高的一种，且呈逐年上升趋势。CHD 严重危害婴幼儿的健康，给家庭和社会带来沉重的经济负担。CHD 的发病机制和预防措施是当前研究的重点。我们的研究旨在探讨围孕期补充叶酸对亚砷酸钠（NaAsO）暴露致心脏畸形的干预作用。
方法：60 只 35 日龄雌性 SD 大鼠随机分为 5 组，每组 12 只。A 组为对照组，给予蒸馏水和普通饲料；B 组给予含 75mg/LNaAsO 的蒸馏水和普通饲料；C、D、E 组给予含 75mg/LNaAsO 的蒸馏水和含 0.53mg/kg、5.3mg/kg、10.6mg/kg 叶酸的饲料。观察胚胎一般情况及胚胎心脏组织病理学变化，检测心脏组织组蛋白 H3K9 乙酰化水平及与心脏发育相关的 Mef2C 表达水平。
结果：B-E 组胚胎体重及胎盘重量均明显低于 A 组（P<0.05），B-E 组胎鼠心脏畸形率明显高于 A 组（P<0.05）。B-E 组胎鼠心肌细胞 H3K9 乙酰化水平明显高于 A 组（P<0.05），C-E 组低于 B 组（P<0.05）。B-E 组胎鼠心肌细胞 Mef2C mRNA 表达水平明显高于 A 组（P<0.05），C-E 组明显低于 B 组（P<0.05）。
结论：围孕期补充叶酸可干预砷对心脏的毒性作用，其机制可能是通过降低心脏组织组蛋白 H3K9 乙酰化水平，导致 Mef2C 表达水平降低，从而对胎鼠心脏发育发挥保护作用。
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