鸢尾素通过促进血管生成而发挥针对心肌梗塞的治疗作用。,Acta Pharmacologica Sinica

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鸢尾素通过促进血管生成而发挥针对心肌梗塞的治疗作用。
Acta Pharmacologica Sinica ( IF 6.9 ) Pub Date : 2019-05-06 , DOI: 10.1038/s41401-019-0230-z
Qiao Liao _{1,

2,

3} , Shuang Qu _{1,

2,

3} , Lu-Xun Tang _{1,

2,

3} , Liang-Peng Li _{1,

2,

3} , Duo-Fen He _{1,

2,

3} , Chun-Yu Zeng _{1,

2,

3} , Wei Eric Wang _{1,

2,

3}

Affiliation

Irisin是一种肌动蛋白，可从骨骼肌和心肌中含有纤连蛋白结构域的5蛋白的胞外部分切割下来，并在运动过程中作为激素分泌到循环系统中。已发现鸢尾素对肺和心脏的损伤具有保护作用。但是，虹膜素是否会影响心肌梗塞（MI）尚不清楚。在这项研究中，我们研究了虹膜素在急性心肌梗死模型中的治疗作用及其潜在机制。成年C57BL / 6小鼠结扎左前降支冠状动脉，并在MI后用虹膜素治疗2周。使用超声心动图评估心脏功能。我们发现，在MI后4周，服用鸢尾素可以显着缓解MI引起的心脏功能障碍和心室扩张。Irisin显着减少MI后心脏的梗塞面积和纤维化。鸢尾素的施用显着增加了梗塞边界区的血管生成，并减少了心肌细胞的凋亡，但不影响心肌细胞的增殖。在人脐静脉内皮细胞（HUVEC）中，虹膜素显着增加了ERK的磷酸化，并促进了在伤口愈合和Transwell室迁移分析中检测到的HUVEC迁移。虹膜素的作用被ERK抑制剂U0126阻断。总之，鸢尾素改善了心梗后小鼠心脏的心脏功能并减小了梗塞面积。通过激活ERK信号传导途径，其治疗作用与其促血管生成功能有关。鸢尾素的施用显着增加了梗塞边界区的血管生成，并减少了心肌细胞的凋亡，但不影响心肌细胞的增殖。在人脐静脉内皮细胞（HUVEC）中，虹膜素显着增加了ERK的磷酸化，并促进了在伤口愈合和Transwell室迁移分析中检测到的HUVEC迁移。虹膜素的作用被ERK抑制剂U0126阻断。总之，鸢尾素改善了心梗后小鼠心脏的心脏功能并减小了梗塞面积。通过激活ERK信号传导途径，其治疗作用与其促血管生成功能有关。鸢尾素的施用显着增加了梗塞边界区的血管生成，并减少了心肌细胞的凋亡，但不影响心肌细胞的增殖。在人脐静脉内皮细胞（HUVEC）中，虹膜素显着增加了ERK的磷酸化，并促进了在伤口愈合和Transwell室迁移分析中检测到的HUVEC迁移。虹膜素的作用被ERK抑制剂U0126阻断。总之，鸢尾素改善了心梗后小鼠心脏的心脏功能并减小了梗塞面积。通过激活ERK信号传导途径，其治疗作用与其促血管生成功能有关。并促进了在伤口愈合和transwell室迁移分析中检测到的HUVEC迁移。虹膜素的作用被ERK抑制剂U0126阻断。总之，鸢尾素改善了心梗后小鼠心脏的心脏功能并减小了梗塞面积。通过激活ERK信号传导途径，其治疗作用与其促血管生成功能有关。并促进了在伤口愈合和transwell室迁移分析中检测到的HUVEC迁移。虹膜素的作用被ERK抑制剂U0126阻断。总之，鸢尾素改善了心梗后小鼠心脏的心脏功能并减小了梗塞面积。通过激活ERK信号传导途径，其治疗作用与其促血管生成功能有关。

"点击查看英文标题和摘要"

Irisin exerts a therapeutic effect against myocardial infarction via promoting angiogenesis.

Irisin, a myokine, is cleaved from the extracellular portion of fibronectin domain-containing 5 protein in skeletal muscle and myocardium and secreted into circulation as a hormone during exercise. Irisin has been found to exert protective effects against lung and heart injuries. However, whether irisin influences myocardial infarction (MI) remains unclear. In this study we investigated the therapeutic effects of irisin in an acute MI model and its underlying mechanisms. Adult C57BL/6 mice were subjected to ligation of the left anterior descending coronary artery and treated with irisin for 2 weeks after MI. Cardiac function was assessed using echocardiography. We found that irisin administration significantly alleviated MI-induced cardiac dysfunction and ventricular dilation at 4 weeks post-MI. Irisin significantly reduced infarct size and fibrosis in post-MI hearts. Irisin administration significantly increased angiogenesis in the infarct border zone and decreased cardiomyocyte apoptosis, but did not influence cardiomyocyte proliferation. In human umbilical vein endothelial cells (HUVEC), irisin significantly increased the phosphorylation of ERK, and promoted the migration of HUVEC detected in wound-healing and transwell chamber migration assay. The effects of irisin were blocked by the ERK inhibitor U0126. In conclusion, irisin improves cardiac function and reduces infarct size in post-MI mouse heart. The therapeutic effect is associated with its pro-angiogenic function through activating ERK signaling pathway.

更新日期：2019-05-16

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