信号转导通路在心肌营养素-1调解心肌转录因子GATA4表达中的作用

目的探讨（CT-1）3条主要作用通路（STAT3、ERK和PI3-K）在其致心肌肥大过程中的作用及相互关系。方法应用Parthenolide（STAT3通路阻断剂）和（或）U0126（ERK通路阻断剂）及（或）LY-294002（PI3-K通路阻断剂）预处理，再加入CT-1（0．1nmol／L）作用6h后测定各组GATA4 mRNA，作用60min后测定GATA4结合活性。结果Parthenohde可抑制CT-1引起的GATA4 mRNA的表达（P〈0.01）及结合活性的增强，U0126可以增加GATA4转录表达（P〈0．01）及GATA4结合活性，LY294002对上述过程均无影响。U0126引起的GATA4的表达增加可被Parthenohde抑制。结论CT-1主要主要通过STAT3通路发挥致肥大作用，ERK通路通过负调节STAT3通路参与CT-1肥大刺激过程，而PI3-K通路则不参与此过程。STAT3与ERK通路的相互作用共同参与CT-1的致肥大过程。

Contributions of signaling pathways on expression of GATA4 induced by CT-1

Objective On the GATA4 level,we assess the contributions and relationships of the three signalling pathways(STAT3,ERK,PI3-K)to the cardiac hypertrophy induced by cardiotrophin-1(CT-1).Methods Using semi-quantitative RT-PCR and EMSA,We measured the GATA4 mRNA and binding activity values of the cultured rat's cardiomyocytes after being treated with 0.1 nmol/L CT-1 for different times.Using Parthenolide(a STAT3 inhibitor),U0126(an inhibitor of ERK)and LY294002(a PI3-K inhibitor)alone or combined with another to assess the contributions of three signalling pathways to the cardiac hypertrophy induced by CT-1.Results Parthenolide reversed the increase of GATA4 mRNA(P <0.01)and binding activity induced by CT-1.U0126 increased the expression of GATA4 mRNA as well as enhanced the GATA4 binding activity.LY294002 had no effect on these processes.Compared with using U0126 alone,the expression of GATA4 mRNA and binding activity dropped significantly when using U0126 and Parthenolide together,but GATA4 mRNA had no change when using U0126 and LY294002(P > 0.05).Conclusions STAT3 plays a primary role in cardiac hypertrophy induced by CT-1,ERK plays an indirect role in this process through negatively regulating STAT3,and PI3-K does not participate in this process.The intercross relationship between STAT3 and ERK may assist CT-1 in cardiac hypertrophy.