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NOX4\u2010induced ROS activated NLRP3 inflammasome and exacerbates MIRI. This study aims to investigate whether NRG\u20101 can suppress NOX4 by ERK1\/2 and consequently inhibit the NLRP3\/caspase\u20101 signal in MIRI. The myocardial infarct size (IS) was measured by TTC\u2010Evans blue staining. Immunohistochemical staining, real\u2010time quantitative PCR (RT\u2010qPCR) and Western blotting were used for detection of the factors, such as NOX4, ERK1\/2, NLRP3, caspase\u20101 and IL\u20101\u03b2 .The IS in the NRG\u20101 (3\u00a0\u03bcg\/kg, intravenous) group was lower than that in the IR group. Immunohistochemical analysis revealed NRG\u20101 decreased 4HNE and NOX4. The RT\u2010qPCR and Western blot analyses revealed that NRG\u20101 mitigated the IR\u2010induced up\u2010regulation of NOX4 and ROS production. Compared with the IR group, the NRG\u20101 group exhibited a higher level of P\u2010ERK1\/2 and a lower level of NLRP3. In the Langendorff model, PD98059 inhibited ERK1\/2 and up\u2010regulated the expression of NOX4, NLRP3, caspase\u20101 and IL\u20101\u03b2, which exacerbated oxidative stress and inflammation. In conclusion, NRG\u20101 can reduce ROS production by inhibiting NOX4 through ERK1\/2 and inhibit the NLRP3\/caspase\u20101 pathway to attenuate myocardial oxidative damage and inflammation in MIRI.<\/jats:p>","DOI":"10.1111\/jcmm.16287","type":"journal-article","created":{"date-parts":[[2021,1,20]],"date-time":"2021-01-20T14:42:15Z","timestamp":1611153735000},"page":"1783-1795","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Neuregulin\u20101 alleviate oxidative stress and mitigate inflammation by suppressing NOX4 and NLRP3\/caspase\u20101 in myocardial ischaemia\u2010reperfusion injury"],"prefix":"10.1111","volume":"25","author":[{"given":"Fuhua","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Critical Care Medicine The Affiliated Hospital of Qingdao University Qingdao China"},{"name":"Department of Cardiology Peking University Third Hospital Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides Ministry of Health Key Laboratory of Molecular Cardiovascular Sciences Ministry of Education, Beijing Key Laboratory of Cardiovascular Receptors Research Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Wang","sequence":"additional","affiliation":[{"name":"Experimental and Translational Research Center Beijing Friendship Hospital Capital Medical University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuejing","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Fundamental Oncology University of Lausanne Lausanne Switzerland"},{"name":"Ludwig Institute for Cancer Research University of Lausanne Epalinges Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyi","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Cardiology Peking University Third Hospital Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides Ministry of Health Key Laboratory of Molecular Cardiovascular Sciences Ministry of Education, Beijing Key Laboratory of Cardiovascular Receptors Research Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomin","family":"Huang","sequence":"additional","affiliation":[{"name":"The Seventh Affiliated Hospital of Sun Yat\u2010Sen University Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Huang","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences Ministry of Education Peking University Health Science Center Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6890-2495","authenticated-orcid":false,"given":"Guisong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiology Peking University Third Hospital Key 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