摘要
先天性心脏病(先心病)是新生儿第一大出生缺陷,其中主因素有遗传因素、环境因素,但更多的是两者的相互作用。诱发先心病发生的环境因素复杂多样,但是具体的致病机制还有待阐明。研究表明孕母体早期感染流感病毒后,胎儿出现心血管畸形的概率显著增加,但其分子机制尚不明确。为了揭示流感病毒宫内感染和先天性心脏缺陷之间的关系,本实验利用F344 大鼠建立了流感病毒宫内感染的动物模型,观察了感染流感病毒后孕鼠胚胎的发育,并利用荧光定量PCR 检测了调控大鼠胚胎心脏发育的关键基因的表达。结果表明,流感病毒感染孕鼠后延迟鼠的胚胎发育,导致胚胎心脏发育异常。同时,胚胎心脏发育的关键基因骨形成蛋白4 (bone morphogeneticprotein 4, BMP4)、成纤维细胞生长因子12 (fibroblast growth factor 12, FGF12)、包含氧化还原酶的WW 域(WW domain-containing oxidoreductase,WWOX)、盘状结构域受体2 (discoidin domain-containing receptor 2, DDR2)和乙型肾上腺素受体3 (Ephrin type-B receptor 3, EPHB3)的表达下调,且均具有统计学差异。本研究初步证明流感病毒可能通过抑制胚胎心脏发育相关基因的表达,影响胚胎心脏发育过程,致使先心病的发生。
Congenital heart disease(CHD) is one of the most major birth defects in neonates. The causing fac-tors are both genetic and environmental. Clinical survey indicated that maternal influenza viral infection is one of the most important environmental factors, but the specific pathogenesis remains to be elucidated. To explore the relationship between CHD and influenza virus infection, F344 rats were used to establish an an-imal model. Then, rat embryo and heart samples were obtained to observe morphological and structural ab-normalities in H1 N1-infected pregnant rats. Real-time quantitative PCR was performed to analyze the mR-NA levels of cardiac development-related candidate genes in embryonic heart of rats. The results showed that intrauterine influenza virus infection delayed embryonic development and led to cardiac diseaes in rats.Bone morphogenetic protein 4(BMP4), fibroblast growth factor 12(FGF12), WW domain-containing oxidoreductase(WWOX), discoidin domain-containing receptor 2(DDR2) and Ephrin type-B receptor 3(EPHB3)were significantly down-regulated in influenza virus infection group compared with those in the control group. In conclusion, influenza virus infection might influence the development of embryonic heart through down-regulating heart development related genes, thereby inducing CHD.
作者
岳树盛
史艳
向红群
王珩
朱泽曙
丁浩东
范雄伟
吴秀山
李芳
莫小阳
YUE Shu-sheng;SHI Yan;XIANG Hong-qun;WANG Heng;ZHU Ze-shu;DING Hao-dong;FAN Xiong-wei;WU Xiu-shan;LI Fang;MO Xiao-yang(Center of Heart Development,College of Life Sciences,Hunan Normal University,Changsha 410081,Hunan,China)
出处
《生命科学研究》
CAS
CSCD
2019年第4期270-275,296,共7页
Life Science Research
基金
国家自然科学基金资助项目(81670288,81800289)
湖南省自然科学基金青年项目(2019JJ50394)
中国博士后基金面上项目(2017M622583)
关键词
先天性心脏病
流感病毒
大鼠
基因表达
congenital heart disease
influenza virus
rats
gene expression
