天津医药

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柯萨奇B3病毒对心脏发育因子GATA-4、NKx2.5表达的影响及叶酸对其的保护作用

薛雅馨1,仇小强2,3   

  1. 1. 桂林医学院附属医院心内科
    2. 桂林医学院公共卫生学院
    3. 广西医科大学
  • 收稿日期:2013-03-20 修回日期:2013-08-26 出版日期:2013-12-15 发布日期:2013-12-15
  • 通讯作者: 薛雅馨

Protective Effects of Folic Acid on Cardiac Development Related Genes GATA-4and NKx2.5 Expression of Offspring Rats with Maternal Coxsackievirus B3Infection

XUE Ya xin1,QIU Xiao qiang2,3   

  1. 1. Department of Cardiology, Affiliated Hospital of Guilin Medical University
    2. Guangxi Medical University
    3. Public Health School, Guilin Medical University
  • Received:2013-03-20 Revised:2013-08-26 Published:2013-12-15 Online:2013-12-15
  • Contact: XUE Ya xin

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摘要：

【摘要】  目的  探讨叶酸对孕期感染柯萨奇B3病毒(CVB3)的新生鼠心脏发育因子GATA-4、NKx2.5的基因与蛋白表达的影响。  方法  SD雌鼠分为对照组、叶酸组、CVB3组、CVB3+叶酸组。叶酸组及CVB3+叶酸组孕前给予叶酸灌胃2周；CVB3组及CVB3+叶酸组孕第7天腹腔注射CVB3，连续5d，自然分娩后取新生鼠心脏组织，病理切片HE染色观察新生鼠心脏组织形态学变化；逆转录聚合酶链反应（RT-PCR）及Western blot测定新生鼠心脏组织中转录因子GATA-4、NKx2.5基因及蛋白表达水平。 结果  CVB3组新生鼠心肌损伤明显，心肌细胞排列紊乱，心肌纤维断裂，CVB3+叶酸组状态改善。CVB3组新生鼠心脏组织GATA-4、NKx2.5基因及蛋白表达低于对照组（P＜0.05），CVB3+叶酸组GATA-4、NKx2.5基因及蛋白表达高于CVB3组（P＜0.05）。  结论  孕鼠早期感染CVB3抑制新生鼠心脏发育因子正常表达，补充叶酸对新生鼠心脏发育具有明显保护作用。

关键词: 柯萨奇病毒感染, 叶酸, 心脏缺损, 先天性, GATA4转录因子, 逆转录聚合酶链反应, 印迹法, 蛋白质

Abstract:

[Abstract]   Objective   To investigate the effects of oral folic acid on cardiac development related gene expression of
offspring in an experimental model of coxsackievirus B3(CVB3) infection of pregnant rats.   Methods   SD female rats were randomized into control group, folic acid group, CVB3group and CVB3+ folic acid group. The female rats were given folic acid by gavage for2weeks before pregnancy in folic acid group and CVB3+ folic acid group. After conception for7days, rat model was established by intraperitoneal injection of CVB3for5days in CVB3group and CVB3+ folic acid group. After natural childbirth neonatal heart was taken and stored in liquid nitrogen. The morphological changes of neonatal rat myocardial tissues were observed by HE staining. The expressions of GATA-4and NKx2.5mRNA were detected by RT- PCR and Western blot assay.  Results   There was significant myocardial injury, such as myocardial fiber disarray and myocardial fiber breakage, in neonatal rats in CVB3group. These damages were improved in CVB3+ folic acid group. The expression levels of GATA-4and NKx2.5genes in myocardial tissues were significantly lower in CVB3group than those of control group (P<0.05). The expression levels of GATA-4and NKx2.5proteins in myocardial tissues were significantly higher in CVB3+ folic acid group than those of CVB3group (P<0.05).   Conclusion   CVB3infection in the early pregnancy inhibited the expression of neonatal rat cardiac development factor. Folic acid supplementation has obvious protective effects on the neonatal rat cardiac development.

Key words: coxsackievirus infections, folic acid, Heart defect, congenital, GATA4transcription factor, reverse transcriptase polymerase chain reaction, blotting, 蛋白质