{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T20:17:45Z","timestamp":1792268265650,"version":"4.4.0"},"reference-count":44,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,10,6]],"date-time":"2022-10-06T00:00:00Z","timestamp":1665014400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004731","name":"Zhejiang provincial natural science foundation","doi-asserted-by":"publisher","award":["LZ20H010001"],"award-info":[{"award-number":["LZ20H010001"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Zhejiang provincial natural science foundation","doi-asserted-by":"publisher","award":["2018YFA0507700"],"award-info":[{"award-number":["2018YFA0507700"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key R&amp;D Program of China","doi-asserted-by":"publisher","award":["LZ20H010001"],"award-info":[{"award-number":["LZ20H010001"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key R&amp;D Program of China","doi-asserted-by":"publisher","award":["2018YFA0507700"],"award-info":[{"award-number":["2018YFA0507700"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Lung ischemia-reperfusion injury (LIRI) is associated with many diseases, including primary graft dysfunction after lung transplantation, and has no specific and effective therapies. Necroptosis contributes to the pathogenesis of ischemia-reperfusion injury. Necrostatin-1 (Nec-1), the necroptosis inhibitor targeting RIPK1, has been reported to alleviate ischemia-reperfusion injury in various organs. However, the underlying mechanism of Nec-1 in LIRI remains unclear. In this paper, an in vivo LIRI model was built up by left lung hilar clamping in mice, and an in vitro cold ischemia-reperfusion (CI\/R) model using BEAS-2B cells was applied to mimic the lung transplantation setting. We found Nec-1 significantly alleviated ischemia-reperfusion-induced lung injury, cytokine releasing, and necroptosis of epithelial cells in mouse lungs. In vitro, Nec-1 also mitigated CI\/R-induced cell death and inflammatory responses in BEAS-2B cells, and these protective effects were achieved by simultaneously inhibiting the formation of necrosome and RIPK1-dependent apoptosis. However, Nec-1 decreased the necrosome number but increased the apoptosis level in lung tissues after ischemia reperfusion. We further clarified that Nec-1 could also attenuate lung injury by promoting neutrophil apoptosis from flow cytometry. In conclusion, Nec-1 alleviated lung ischemia-reperfusion injury by inhibiting necroptosis and apoptosis of epithelial cells and promoting the apoptosis of neutrophils. Thus, Nec-1 could be a promising medication against primary graft dysfunction after lung transplantation.<\/jats:p>","DOI":"10.3390\/cells11193139","type":"journal-article","created":{"date-parts":[[2022,10,8]],"date-time":"2022-10-08T01:52:21Z","timestamp":1665193941000},"page":"3139","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Necrostatin-1 Alleviates Lung Ischemia-Reperfusion Injury via Inhibiting Necroptosis and Apoptosis of Lung Epithelial Cells"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1565-6083","authenticated-orcid":false,"given":"Lingjun","family":"Dong","sequence":"first","affiliation":[{"name":"Department of Thoracic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3420-6763","authenticated-orcid":false,"given":"Fuxiang","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2223-1462","authenticated-orcid":false,"given":"Zhiling","family":"Lou","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangfan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinsheng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3158-3424","authenticated-orcid":false,"given":"Yaling","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Basic Medical Sciences, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Basic Medical Sciences, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuanqiang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yafei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Basic Medical Sciences, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6539-4798","authenticated-orcid":false,"given":"Yunbi","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Basic Medical Sciences, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1009-5387","authenticated-orcid":false,"given":"Ming","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China"},{"name":"Key Laboratory of The Diagnosis and Treatment of Severe Trauma and Burn of Zhejiang Province, Hangzhou 310009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1016\/j.healun.2017.07.020","article-title":"Report of the International Society for Heart and Lung Transplantation Working Group on Primary Lung Graft Dysfunction, part II: Epidemiology, risk factors, and outcomes\u2014A 2016 Consensus Group statement of the International Society for Heart and Lung Transplantation","volume":"36","author":"Diamond","year":"2017","journal-title":"J. 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