[中文]大量的研究表明内皮向间质转化（EndMT）在纤维化疾病中发挥重要作用。本次研究的目的是探究EndMT是否参与了三氧化二砷诱发的心肌纤维化，并探究其内在机制。超声心动图结果显示大鼠在给予三氧化二砷15天之后出现了明显的心脏功能障碍，并且马桑染色和电解结果显示心脏组织间和血管周围出现了大量的胶原沉积。RT-PCR, Western Blot 和免疫荧光结果显示心肌组织内内皮细胞标志物（VE-cadherin and CD31）表达下调，间质细胞标志物（α-SMA and FSP）表达上调，意味着发生了EndMT。体内实验表明内皮细胞在给予三氧化二砷处理之后其形态由卵圆形变成了长梭形，并伴随着内皮细胞标志物的下调和间质细胞标志物的上调，同时三氧化二砷的给予激活了AKT/GSK-3β/Snail信号通路，而采用PI3K的抑制剂抑制这一通路后，EndMT的现象也受到抑制。我们的结果表明三氧化二砷可通过EndMT诱导心肌纤维化，靶向EndMT可改善三氧化二砷诱导的心脏毒性。[/中文]

[外文]Emerging evidence has suggested the critical role of endothelial to mesenchymal transition (EndMT) in fibrotic diseases. The present study was designed to examine whether EndMT is involved in arsenic trioxide (As2O3)-induced cardiac fibrosis and to explore the underlying mechanisms. Cardiac dysfunction was observed in rats after exposure to As2O3 for 15 days using echocardiography, and the deposition of collagen was detected by Masson′s trichrome staining and electron microscope. EndMT was indicated by the loss of endothelial cell markers (VE-cadherin and CD31) and the acquisition of mesenchymal cell markers (α-SMA and FSP1) determined by RT-PCR at the mRNA level and Western blot and immunofluorescence analysis at the protein level. In the in-vitro experiments, endothelial cells acquired a spindle-shaped morphology accompanying downregulation of the endothelial cell markers and upregulation of the mesenchymal cell markers when exposed to As2O3. As2O3 activated the AKT/GSK-3β/Snail signaling pathway, and blocking this pathway with PI3K inhibitor (LY294000) abolished EndMT in As2O3-treated endothelial cells. Our results highlight that As2O3 is an EndMT-promoting factor during cardiac fibrosis, suggesting that targeting EndMT is beneficial for preventing As2O3-induced cardiac toxicity.[/外文]