Interleukin-12p35 Knock Out Aggravates Doxorubicin-Induced Cardiac Injury and Dysfunction by Aggravating the Inflammatory Response, Oxidative Stress, Apoptosis and Autophagy in Mice
机构：[a]Department of Cardiology, Renmin Hospital ofWuhan University, Cardiovascular Research Institute, Wuhan University, Hubei Key Laboratory of Cardiology, Wuhan 430060, China[b]Department of Cardiology, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, China[c]Department of Ultrasound, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, China[d]Emergency & Critical Care Center, Beijing Anzhen Hospital, Capital Medical University, and Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing 100029, China临床科室急诊危重症中心首都医科大学附属安贞医院[e]Department of Cardiology, Handan First Hospital, Handan 056002, China
Background: Recent evidence has demonstrated that interleukin 12p35 knockout (IL-12p35 KO) is involved in cardiac diseases by regulating the inflammatory response. The involvement of inflammatory cells has also been observed in doxorubicin (DOX)-induced cardiac injury. This study aimed to investigate whether IL-12p35 KO affects DOX-induced cardiac injury and the underlying mechanisms. Methods: First, the effect of DOX treatment on cardiac IL-12p35 expression was assessed. In addition, to investigate the effect of IL-12p35 KO on DOX-induced cardiac injury, IL-12p35 KO mice were treated with DOX. Because IL-12p35 is the mutual subunit of IL-12 and IL-35, to determine the cytokine that mediates the effect of IL-12p35 KO on DOX-induced cardiac injury, mice were given phosphate-buffered saline (PBS), mouse recombinant IL-12 ( rIL-12) or rIL-35 before treatment with DOX. Results: DOX treatment significantly increased the level of cardiac IL-12p35 expression. In addition, IL-12p35 KO mice exhibited higher serum and heart lactate dehydrogenase levels, higher serum and heart creatine kinase myocardial bound levels, and greater cardiac dysfunction than DOX-treated mice. Furthermore. IL-12p35 KO further increased M1 macrophage and decreased M2 macrophage differentiation, aggravated the imbalance of oxidants and antioxidants, and further activated the mitochondrial apoptolic pathway and endoplasmic reticulum stress autophagy pathway. Both rIL-12 and rIL-35 protected against DOX-induced cardiac injury by alleviating the inflammatory response, oxidative stress, apoptosis and autophagy. Conclusions: IL-12p35 KO aggravated DOX-induced cardiac injury by amplifying the levels of inflammation, oxidative stress, apoptosis and autophagy. (234 words). (C) 2018 The Authors. Published by Elsevier B.V.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81770472, 81460081, 81460061, 81760051]
第一作者机构：[a]Department of Cardiology, Renmin Hospital ofWuhan University, Cardiovascular Research Institute, Wuhan University, Hubei Key Laboratory of Cardiology, Wuhan 430060, China[b]Department of Cardiology, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, China[d]Emergency & Critical Care Center, Beijing Anzhen Hospital, Capital Medical University, and Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing 100029, China
共同第一作者：
通讯作者：
通讯机构：[a]Department of Cardiology, Renmin Hospital ofWuhan University, Cardiovascular Research Institute, Wuhan University, Hubei Key Laboratory of Cardiology, Wuhan 430060, China[b]Department of Cardiology, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, China[d]Emergency & Critical Care Center, Beijing Anzhen Hospital, Capital Medical University, and Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing 100029, China[*1]Department of Cardiology, Renmin Hospital ofWuhanUniversity, Cardiovascular Research Institute,WuhanUniversity,Hubei Key Laboratory of Cardiology, Wuhan 430060, China.
推荐引用方式(GB/T 7714)：
Jing Ye,Ying Huang,Bin Que,et al.Interleukin-12p35 Knock Out Aggravates Doxorubicin-Induced Cardiac Injury and Dysfunction by Aggravating the Inflammatory Response, Oxidative Stress, Apoptosis and Autophagy in Mice[J].EBIOMEDICINE.2018,35:29-39.doi:10.1016/j.ebiom.2018.06.009.
APA：
Jing Ye,Ying Huang,Bin Que,Chao Chang,Wenjing Liu...&Qingwei Ji.(2018).Interleukin-12p35 Knock Out Aggravates Doxorubicin-Induced Cardiac Injury and Dysfunction by Aggravating the Inflammatory Response, Oxidative Stress, Apoptosis and Autophagy in Mice.EBIOMEDICINE,35,
MLA：
Jing Ye,et al."Interleukin-12p35 Knock Out Aggravates Doxorubicin-Induced Cardiac Injury and Dysfunction by Aggravating the Inflammatory Response, Oxidative Stress, Apoptosis and Autophagy in Mice".EBIOMEDICINE 35.(2018):29-39
医学