先天性心脏病胎儿心脏及胎盘组织中MAPK及Akt信号通路分子的变化

Changes of MAPK and Akt signaling pathways in hearts and placentas of aborted fetuses with congenital heart disease

摘要:

目的：检测先天性心脏病(congenital heart disease，CHD)胎儿心脏及胎盘组织中MAPK及Akt信号通路分子表达变化，探讨其在CHD发病过程中的作用。方法：选取10例因患严重CHD/或同时伴其他缺陷而引产的胎儿，采用Western blot技术检测心脏左心室及胎盘组织中p38、p38α、p-p38、MEF2、ERK、p-ERK Akt、p-AktSer473、p-AktThr308蛋白表达量，采用半定量RT-PCR方法检测左心室p38α mRNA水平。7例孕龄相似、无CHD畸形儿为对照组。结果：①Western blot结果示：与对照组相比，CHD组中分别有4例心脏组织中p38及其亚型p38α、6例p-p38、2例MEF2、8例p-ERK、4例Akt及8例p-AktSer473和p-AktThr308蛋白水平降低，2例p-p38及1例p-AktThr308升高；CHD组中3例胎盘组织中p-p38上升，2例p-ERK下降。②CHD组MAPK及Akt信号通路蛋白表达量在胎儿心脏与胎盘组织中的变化不一致。③与对照组相比，4例p38α蛋白减少的心脏样本p38α异构体2 mRNA水平均降低，只有1例p38α异构体1、3、4 mRNA也减少。结论：CHD胎儿MAPK及Akt信号通路分子蛋白表达变化具有组织特异性，心脏组织中MAPK及Akt信号通路的异常可能与人类CHD的发生有关。［中国当代儿科杂志，2010，12（5）：327-332］

Abstract:

OBJECTIVE: To study the changes of MAPK and Akt signaling pathways in hearts and placentas of aborted fetuses with congenital heart disease (CHD), and investigate their roles in the pathogenesis of CHD. METHODS: Ten aborted fetuses with severe CHD (CHD group) and 7 gestational age-matched non-cardiac malformation aborted fetuses (control group) were enrolled. Western blot analysis was undertaken to assess the expression of p38, p38α, p-p38, MEF2, ERK, p-ERK, Akt, p-AktSer473 and p-AktThr308 in left ventricles and placentas of the fetuses, while semi-quantitative reverse transcription polymerase chain reaction analysis was used to detect the expression of p38α isoforms mRNA in hearts. RESULTS: Compared with the heart samples of the control group, the protein expression levels of p38 and its α isoform in 4 cases, p-p38 in 6 cases, MEF2 in 2 cases, p-ERK in 8 cases, Akt in 4 cases, p-AktSer473 and p-AktThr308 in 8 cases decreased, while the protein expression levels of p-p38 in 2 cases and p-AktThr308 in 1 case increased. P-p38 protein level in 3 cases and p-ERK protein level in 2 cases decreased in placentas compared with the control group. The changes of protein expression of MAPK and Akt signaling pathway in hearts were not consistent with those in placentas in the CHD group. The expression of p38α isoform2 mRNA showed descent tendency in 4 heart samples with CHD, while the expression of other three p38α isoforms mRNA was reduced in only 1 sample compared with the control group. CONCLUSIONS: Dysfunction of MAPK and Akt signaling pathways is tissue-specific in aborted fetuses with CHD. The perturbed two signaling pathways in hearts may contribute to the pathogenesis of human CHD.［Chin J Contemp Pediatr, 2010, 12 (5):327-332］