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Study on Protection of Human Umbilical Vein Endothelial Cells from Amiodarone‐Induced Damage by Intermedin through Activation of Wnt/β‐Catenin Signaling Pathway

作者:Yanhong Wang, Juanjuan Wang, Jia Yang, Jing Kang, Fuping Xue, Sijia Chang, Ji He, Haojing Zang, Xiaoshuang Zhou, Guiqin Wang, Weiping Fan, Xian‐Yan Yan, Jinli Guo, Xiaojun Ren, Jihua Tian · 发表于:Oxidative Medicine and Cellular Longevity · 年份:2021 · DOI:10.1155/2021/8889408 · 被引用次数:10 · 研究领域:Toxin Mechanisms and Immunotoxins、Signaling Pathways in Disease、Neuropeptides and Animal Physiology

Amiodarone (AM) is one of the most effective antiarrhythmic drugs and normally administrated by intravenous infusion which is liable to cause serious phlebitis. The therapeutic drugs for preventing this complication are limited. Intermedin (IMD), a member of calcitonin family, has a broad spectrum of biological effects including anti‐inflammatory effects, antioxidant activities, and antiapoptosis. But now, the protective effects of IMD against amiodarone‐induced phlebitis and the underlying molecular mechanism are not well understood. In this study, the aim was to investigate the protective efficiency and potential mechanisms of IMD in amiodarone‐induced phlebitis. The results of this study revealed that treatment with IMD obviously attenuated apoptosis and exfoliation of vascular endothelial cells and infiltration of inflammatory cells in the rabbit model of phlebitis induced by intravenous infusion of amiodarone compared with control. Further tests in vitro demonstrated that IMD lessened amiodarone‐induced endothelial cell apoptosis, improved amiodarone‐induced oxidative stress injury, reduced inflammatory reaction, and activated the Wnt/ β ‐catenin signal pathway which was inhibited by amiodarone. And these effects could be reversed by Wnt/ β ‐catenin inhibitor IWR‐1‐endo, and si‐RNA knocked down the gene of Wnt pathway. These results suggested that IMD exerted the protective effects against amiodarone‐induced endothelial injury via activating the Wnt/ β ‐catenin pathway. ...