PMID- 28316125 OWN - NLM STAT- MEDLINE DCOM- 20180205 LR - 20181202 IS - 1748-1716 (Electronic) IS - 1748-1708 (Linking) VI - 221 IP - 2 DP - 2017 Oct TI - Deferoxamine-activated hypoxia-inducible factor-1 restores cardioprotective effects of sevoflurane postconditioning in diabetic rats. PG - 98-114 LID - 10.1111/apha.12874 [doi] AB - AIM: The cardioprotective effects of sevoflurane postconditioning (SpostC) are eliminated under diabetic conditions, and the underlying mechanism for this phenomenon remains unclear. Many studies have demonstrated that the hypoxia-inducible factor-1 (HIF-1) signalling pathway in the myocardium is impaired under diabetic conditions. This study was to investigate whether deferoxamine (DFO)-induced activation of HIF-1 signalling pathway can restore the cardioprotective effects of SpostC in diabetic rats. METHODS: A model of myocardial ischaemia/reperfusion (I/R) injury was induced via ligation of the left anterior descending artery. SpostC was conducted by administering 1.0 MAC sevoflurane. After inducing the I/R injury, the following parameters were measured: myocardial infarct size, cardiac function, myocardial ultrastructure, mitochondrial respiratory function, respiratory chain enzyme activity, rate of reactive oxygen species (ROS) generation, and protein expression of HIF-1alpha, vascular endothelial growth factor (VEGF), cleaved caspase-3, Bcl-2 and Bax. RESULTS: After DFO activated HIF-1 in the impaired myocardium of diabetic rats, SpostC significantly upregulated the protein expression of HIF-1alpha and its downstream mediator VEGF. This improved myocardial mitochondrial respiratory function and respiratory chain enzyme activity and reduced ROS generation as well as the protein expression of cleaved caspase-3 and Bax. As a result, myocardial infarct size decreased, and cardiac function and mitochondrial ultrastructure improved. CONCLUSION: This study demonstrates for the first time that abolishment of the cardioprotective effects of SpostC in diabetic rats is associated with impairment of the HIF-1 signalling pathway and that DFO can activate HIF-1 to restore these cardioprotective effects of SpostC in diabetic rats. CI - (c) 2017 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd. FAU - Xie, P AU - Xie P AD - Department of Anesthesiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China. FAU - Yang, L AU - Yang L AD - Department of Anesthesiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China. FAU - Talaiti, A AU - Talaiti A AD - Department of Anesthesiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China. FAU - Wu, J J AU - Wu JJ AD - Department of Anesthesiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China. FAU - Yu, J AU - Yu J AD - Department of Anesthesiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China. FAU - Yu, T AU - Yu T AD - Department of Anesthesiology and Guizhou Key Laboratory of Anesthesia and Organ Protection, Zunyi Medical University, Zunyi, Guizhou, China. FAU - Wang, H Y AU - Wang HY AD - Department of Anesthesiology and Guizhou Key Laboratory of Anesthesia and Organ Protection, Zunyi Medical University, Zunyi, Guizhou, China. FAU - Huang, B AU - Huang B AD - Key Lab for Pharmacology of Ministry of Education, Department of Pharmacology, Zunyi Medical University, Zunyi, China. FAU - Wu, Q AU - Wu Q AD - Key Lab for Pharmacology of Ministry of Education, Department of Pharmacology, Zunyi Medical University, Zunyi, China. FAU - Maimaitili, Y AU - Maimaitili Y AD - Department of Anesthesiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China. FAU - Wang, J AU - Wang J AD - Department of Anesthesiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China. FAU - Ma, H P AU - Ma HP AD - Department of Anesthesiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China. FAU - Yang, Y N AU - Yang YN AD - Department of Cardiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China. FAU - Zheng, H AU - Zheng H AD - Department of Anesthesiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China. LA - eng PT - Journal Article DEP - 20170515 PL - England TA - Acta Physiol (Oxf) JT - Acta physiologica (Oxford, England) JID - 101262545 RN - 0 (Anesthetics, Inhalation) RN - 0 (Hypoxia-Inducible Factor 1) RN - 0 (Hypoxia-Inducible Factor 1, alpha Subunit) RN - 0 (Methyl Ethers) RN - 0 (Siderophores) RN - 38LVP0K73A (Sevoflurane) RN - J06Y7MXW4D (Deferoxamine) SB - IM CIN - Acta Physiol (Oxf). 2017 Oct;221(2):93-94. PMID: 28581154 MH - Anesthetics, Inhalation/pharmacology MH - Animals MH - Deferoxamine/*pharmacology MH - Diabetes Mellitus, Experimental/metabolism MH - Gene Expression Regulation/drug effects MH - Hypoxia-Inducible Factor 1/genetics/*metabolism MH - Hypoxia-Inducible Factor 1, alpha Subunit/metabolism MH - *Ischemic Postconditioning MH - Male MH - Methyl Ethers/*pharmacology MH - Myocardial Infarction/metabolism MH - Myocardial Reperfusion Injury/*drug therapy MH - Rats MH - Rats, Sprague-Dawley MH - Sevoflurane MH - Siderophores/pharmacology MH - Signal Transduction MH - Up-Regulation OTO - NOTNLM OT - deferoxamine OT - diabetes OT - hypoxia-inducible factor-1 OT - myocardial protection OT - sevoflurane postconditioning EDAT- 2017/03/21 06:00 MHDA- 2018/02/06 06:00 CRDT- 2017/03/20 06:00 PHST- 2016/12/25 00:00 [received] PHST- 2017/01/29 00:00 [revised] PHST- 2017/03/10 00:00 [revised] PHST- 2017/03/13 00:00 [accepted] PHST- 2017/03/21 06:00 [pubmed] PHST- 2018/02/06 06:00 [medline] PHST- 2017/03/20 06:00 [entrez] AID - 10.1111/apha.12874 [doi] PST - ppublish SO - Acta Physiol (Oxf). 2017 Oct;221(2):98-114. doi: 10.1111/apha.12874. Epub 2017 May 15.