{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T11:37:22Z","timestamp":1789213042431,"version":"build-2803163510"},"reference-count":42,"publisher":"Portland Press Ltd.","issue":"10","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2016,5,1]]},"abstract":"<jats:p>Isoflurane postconditioning (IsoPostC) attenuates myocardial ischaemia\/reperfusion injury (IRI). Signal transducer and activator of transcription-3 (STAT3) is critical in ischaemic postconditioning cardioprotection, which can be regulated by the Brahma-related gene (Brg1) and nuclear factor-erythroid 2-related factor 2 (Nrf2), although they are both reduced in diabetic hearts. We hypothesized that reduced Brg1\/Nrf2 and STAT3 activation may jeopardize IsoPostC-mediated cardioprotection in diabetic hearts. In the present study, Langendorff-perfused, non-diabetic (control) and 8-week-old streptozotocin-induced Type\u00a01 diabetic rat hearts were subjected to 30\u00a0min of global ischaemia and 120\u00a0min of reperfusion without or with IsoPostC, which was achieved by administering emulsified isoflurane (2.0%, v\/v) in Krebs\u2013Henseleit (KH) solution immediately at the onset of reperfusion for 10\u00a0min and switching to KH solution perfusion alone thereafter. Cultured H9C2 cells were exposed to normal glucose (NG, 5.5\u00a0mM) or high glucose (HG, 30\u00a0mM) and subjected to hypoxia\/reoxygenation (HR) in the presence or absence of IsoPostC. Diabetic rats displayed larger post-ischaemic myocardial infarction and more severe haemodynamic dysfunction, associated with increased myocardial oxidative stress and reduced cardiac Brg1, Nrf2 and STAT3 phosphorylation\/activation (p-STAT3), compared with controls. These changes were reversed\/prevented by IsoPostC in control but not in diabetic rats. In H9C2 cells exposed to NG but not HG, IsoPostC significantly attenuated HR-induced cellular injury and superoxide anion production with increased Brg1, Nrf2 and p-STAT3. These beneficial effects of IsoPostC were abolished by Brg1, Nrf2 or STAT3 gene knockdown. Brg1 or Nrf2 gene knockdown abolished IsoPostC-induced STAT3 activation. N-acetylcysteine restored Brg1, Nrf2 and p-STAT3, and IsoPostC-induced protection in H9C2 cells exposed to HG and HR. In conclusion, IsoPostC confers cardioprotection through Brg1\/Nrf2\/STAT3 signalling, and impairment of this pathway may be responsible for the loss of IsoPostC cardioprotection in diabetes.<\/jats:p>","DOI":"10.1042\/cs20150617","type":"journal-article","created":{"date-parts":[[2016,2,5]],"date-time":"2016-02-05T02:13:50Z","timestamp":1454638430000},"page":"801-812","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Cardioprotection from emulsified isoflurane postconditioning is lost in rats with streptozotocin-induced diabetes due to the impairment of Brg1\/Nrf2\/STAT3 signalling"],"prefix":"10.1042","volume":"130","author":[{"given":"Yan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Anaesthesiology, University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haobo","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology, University of Hong Kong, Hong Kong SAR, China"},{"name":"State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huansen","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology, Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiming","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology, Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowen","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology, University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology, Guangdong Cardiovascular Institute and Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanley\u00a0Sau-ching","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology, University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengyuan","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology, University of Hong Kong, Hong Kong SAR, China"},{"name":"State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael\u00a0G.","family":"Irwin","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology, University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2016,4,1]]},"reference":[{"key":"2021113010404782500_B1","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1016\/j.beem.2009.01.003","article-title":"Diabetes and acute coronary syndromes","volume":"23","author":"Roffi","year":"2009","journal-title":"Best Pract. 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