{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:16:38Z","timestamp":1791918998966,"version":"4.3.4"},"reference-count":45,"publisher":"Walter de Gruyter GmbH","issue":"1","license":[{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,10,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Activation of the complement component 5a (C5a) and nuclear factor \u03baB (NF-\u03baB) signaling is an important feature of myocardial ischemia\/reperfusion (I\/R) injury and recent studies show that morphine postconditioning (MP) attenuates the myocardial injury. However, the mediating cardioprotective mechanisms remain unclear. The present study explores the role and interaction of heat shock protein 90 (HSP90), Akt, C5a, and NF-\u03baB in MP-induced cardioprotection.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Male Sprague Dawley rats (<jats:italic>n<\/jats:italic> = 160) were randomized into eight groups (<jats:italic>n<\/jats:italic> = 20 per group). Rats in the sham group underwent thoracotomy, passing the ligature through the heart but without tying it (150\u2009min), and the other seven groups were subjected to 30\u2009min of anterior descending coronary artery occlusion followed by 2\u2009h of reperfusion and the following treatments: I\/R (30\u2009min of ischemia and followed by 2\u2009h of reperfusion); ischemic postconditioning (IPostC, 30\u2009s of ischemia altered with 30\u2009s of reperfusion, repeated for three cycles, and followed by reperfusion for 2\u2009h); MP (0.3\u2009mg\/kg morphine administration 10\u2009min before reperfusion); MP combined with the HSP90 inhibitor geldanamycin (GA, 1\u2009mg\/kg); MP combined with the Akt inhibitor GSK-690693 (GSK, 20\u2009mg\/kg); and MP combined with the C5a inhibitor PMX205 (PMX, 1\u2009mg\/kg\/day, administration via drinking water for 28 days) and MP combined with the NF-\u03baB inhibitor EVP4593 (QNZ, 1\u2009mg\/kg). All inhibitors were administered 10\u2009min before morphine and followed by 2\u2009h reperfusion.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>MP significantly reduced the I\/R-induced infarct size, the apoptosis, and the release of cardiac troponin I, lactate dehydrogenase (LDH), and creatine kinase-MB. These beneficial effects were accompanied by increased expression of HSP90 and p-Akt, and decreased expression of C5a, NF-\u03baB, tumor necrosis factor \u03b1, interleukin-1\u03b2, and intercellular cell adhesion molecule 1. However, HSP90 inhibitor GA or Akt inhibitor GSK increased the expression of C5a and NF-\u03baB and prevented MP-induced cardioprotection. Furthermore, GA inhibited the MP-induced upregulation of p-Akt, while GSK did not affect HSP90, indicating that p-Akt acts downstream of HSP90 in MP-induced cardioprotection. In addition, C5a inhibitor PMX enhanced the MP-induced downregulation of NF-\u03baB, while NF-\u03baB inhibitor QNZ had no effect on C5a, indicating that the C5a\/NF-\u03baB signaling pathway is involved in MP-induced cardioprotection.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>HSP90 is critical for MP-mediated cardioprotection possibly by promoting the phosphorylation of Akt and inhibiting the activation of C5a and NF-\u03baB signaling and the subsequent myocardial inflammation, ultimately attenuating the infarct size and cardiomyocyte apoptosis.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1515\/med-2021-0340","type":"journal-article","created":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T01:52:54Z","timestamp":1634781174000},"page":"1552-1563","source":"Crossref","is-referenced-by-count":8,"title":["New targets of morphine postconditioning protection of the myocardium in ischemia\/reperfusion injury: Involvement of HSP90\/Akt and C5a\/NF-\u03baB"],"prefix":"10.1515","volume":"16","author":[{"given":"Rong-Hui","family":"Tu","sequence":"first","affiliation":[{"name":"Department of Geriatric Cardiology, First Affiliated Hospital, Guangxi Medical University , 6 Shuangyong Road , Nanning , 530021, Guangxi , China"},{"name":"Guangxi Key Laboratory of Precision Medicine in Cardio-Cerebrovascular Diseases Control and Prevention, First Affiliated Hospital, Guangxi Medical University , Nanning , 530021, Guangxi , China"},{"name":"Guang Xi Clinical Research Center for Cardio-Cerebrovascular Diseases, First Affiliated Hospital, Guangxi Medical University , Nanning , 530021, Guangxi , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Xiao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, First Affiliated Hospital, Guangxi Medical University , Nanning , 530021 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo-Qiang","family":"Zhong","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Precision Medicine in Cardio-Cerebrovascular Diseases Control and Prevention, First Affiliated Hospital, Guangxi Medical University , Nanning , 530021, Guangxi , China"},{"name":"Guang Xi Clinical Research Center for Cardio-Cerebrovascular Diseases, First Affiliated Hospital, Guangxi Medical University , Nanning , 530021, Guangxi , China"},{"name":"Department of Cardiology, First Affiliated Hospital, Guangxi Medical University , Nanning , 530021 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Jun","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Geriatric Cardiology, First Affiliated Hospital, Guangxi Medical University , 6 Shuangyong Road , Nanning , 530021, Guangxi , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Geriatric Cardiology, First Affiliated Hospital, Guangxi Medical University , 6 Shuangyong Road , Nanning , 530021, Guangxi , China"},{"name":"Departments of Geriatric Health Care Center, First Affiliated Hospital, Guangxi Medical University , Nanning , 530021, Guangxi , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Jie-Feng","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Science, Guangxi Medical University , Nanning , 530021, Guangxi , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Bi","sequence":"additional","affiliation":[{"name":"Department of Cardiology, First Affiliated Hospital, Guangxi Medical University , Nanning , 530021 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"He","sequence":"additional","affiliation":[{"name":"Department of Geriatric Cardiology, First Affiliated Hospital, Guangxi Medical University , 6 Shuangyong Road , Nanning , 530021, Guangxi , China"},{"name":"Guangxi Key Laboratory of Precision Medicine in Cardio-Cerebrovascular Diseases Control and Prevention, First Affiliated Hospital, Guangxi Medical University , Nanning , 530021, Guangxi , China"},{"name":"Guang Xi Clinical Research Center for Cardio-Cerebrovascular Diseases, First Affiliated Hospital, Guangxi Medical University , Nanning , 530021, Guangxi , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2021,10,18]]},"reference":[{"key":"2022091918195008547_j_med-2021-0340_ref_001","doi-asserted-by":"crossref","unstructured":"Zhang S, Zhou Y, Zhao L, Tian X, Jia M, Gu X, et al. 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