GATA-4在HCY诱导鼠胚心脏畸形中的表达及意义

目的探讨锌指转录因子GATA-4在同型半胱氨酸（Homocysteine,HCY）诱导的大鼠胚胎发育畸形心脏的表达水平及相关意义。方法SD成年健康清洁级雌、雄大鼠各16只,常规方法交配获取孕鼠后,随机分为2组：1正常对照组,2HCY组。各组孕鼠分别于妊娠第13、15、17、19天剖腹取出胚胎,通过切片进行胎鼠心脏组织学观察以确定心脏畸形情况,并通过RT-PCR法半定量测定胎心GATA-4因子mRNA表达。结果HCY组不良胚胎率及胚胎心脏畸形率与对照组相比均显著增高（P〈0.001）;HCY组各妊娠天数胎鼠心脏GATA-4因子mRNA表达均较对照组减少,但无统计学意义（P〉0.05）;而心脏发育畸形胎鼠的心脏GATA-4因子mRNA表达比心脏发育正常胎鼠明显降低（P〈0.001）。结论HCY诱导的孕鼠不良胚胎率及胚胎心脏畸形率均明显增高,且胎鼠畸形心脏组织中GATA-4表达下调,表明锌指转录因子GATA-4的心脏表达抑制与HCY对大鼠胚胎心脏的毒性作用之间存在重要关系。

Heart defects in rat embryos induced by HCY and the fetal heart GATA - 4 expression

Objective ： To explore the relation of the heart malformations in rat embryo reduced by homocysteine and the fetal heart GATA -4 expression. Method： Sprague -Dawley female rats were randomized into control group （C） , homocysteine group （H）, （n = 8 for all） after mating with male counterparts to access to pregnancy. Fetuses from every two of the pregnant rats in each group were acquired by caesarean section after maternal anesthetization at GD 13, 15, 17 and 19, and histologically examined for cardiac malfor- mation. GATA -4 mRNA expression in maternal peripharel lymphocytes was semi -quantified by RT- PCR. Results： The principle menifestations of cardiac anomalies consisted of gross deformity, hypoevolutism, atrial absence, interventrieular septal defect and ven- tricular defect. Prevalence of cardiac malformation was significantly increased in group H versus group C （ P 〈 0. 001 ） , There was slight change in the expression of fetal heart GATA - 4 - mRNA in each group, which was no significant difference （ P 〉 0. 05 ）. At the time points observed, GATA -4 mRNA level was significantly decreased in the embryonic heart defects rats versus the normal heart rats. （ P 〈 0. 001 ）. Conclusion： There is significantly teratogenic effect to embryonic rats in gestational age inject HCY , and observed GATA -4 mRNA level was significantly decreased in the embryonic heart defects rats versus the normal heart rats. These data indicated that alterations in gene regulation might be an underlying mechanism of cardiac abnormalities related with HCY.