Abstract：
Ischemic heart disease is caused by coronary artery occlusion. Despite the increasing number and success of interventions for restoring coronary artery perfusion, myocardial ischemia-reperfusion (I/R) injury remains a significant cause of morbidity and mortality worldwide. Inspired by the impact of I/R on the Cx43 trafficking to the intercalated discs (ICDs), we aim to explore the potential mechanisms underlying the downregulation of Cx43 in ICDs after myocardial I/R. Gene set enrichment analysis (GSEA), Western blotting, and immunofluorescence experiments showed that Myocardial I/R activated the P38MAPK signaling pathway and promoted microtubule depolymerization. Inhibition of P38MAPK signaling pathway activation attenuated I/R-induced microtubule depolymerization. The ability of SB203580 to recover the distribution of Cx43 and electrophysiological parameters in I/R myocardium depended on microtubule stability. Our study suggests that microtubule depolymerization caused by the activation of the P38MAPK signaling pathway is an important mechanism underlying the downregulation of Cx43 in ICDs after myocardial I/R.
摘要：
缺血性心脏病是由冠状动脉闭塞引起的。尽管恢复冠状动脉灌注的干预措施越来越多，也越来越成功，心肌缺血再灌注(I/R)损伤仍是全球范围内发病率和死亡率的重要原因.受I/R对Cx43运输到插层光盘（ICD）的影响的启发，我们旨在探讨心肌I/R后ICD中Cx43下调的潜在机制。基因集富集分析(GSEA),西方印迹,和免疫荧光实验表明，心肌I/R激活了P38MAPK信号通路，促进了微管解聚。P38MAPK信号通路激活的抑制减弱了I/R诱导的微管解聚。SB203580恢复I/R心肌中Cx43分布和电生理参数的能力取决于微管稳定性。我们的研究表明，由P38MAPK信号通路激活引起的微管解聚是心肌I/R后ICD中Cx43下调的重要机制。
