Mechanism of the hypoxia inducible factor 1/hypoxic response element pathway in rat myocardial ischemia/diazoxide post‑conditioning

作者：Jin Li, Wenjing Zhou, Wei Chen, Haiying Wang, Yu Zhang, Tian Yu · 发表于：Molecular Medicine Reports · 年份：2020 · DOI：10.3892/mmr.2020.10966 · 被引用次数：34 · 研究领域：Cardiac Ischemia and Reperfusion、Cardiac Arrest and Resuscitation、Mechanical Circulatory Support Devices

Ischemic post‑conditioning (IPO) and diazoxide post‑conditioning (DPO) has been proven to reduce myocardial ischemia reperfusion injury (MIRI); however, the mechanisms of IPO/DPO are still not clear. The present study aimed to investigate whether mitochondrial ATP‑sensitive potassium channels (mitoKATP) channels are activated by IPO/DPO, which may further activate the hypoxia inducible factor 1/hypoxic response element (HIF‑1/HRE) pathway to mitigate MIRI. Using a Langendorff perfusion device, healthy male (250‑300 g) Sprague Dawley rat hearts were randomly divided into the following groups. Group N was aerobically perfused with K‑H solution for 120 min. Group ischaemia/reperfusion (I/R) was aerobically perfused for 20 min, then subjected to 40 min hypoxia plus 60 min reperfusion. Group IPO was treated like the I/R group, but with 10 sec of hypoxia plus 10 sec of reperfusion for six rounds before reperfusion. Group DPO was exposed to 50 µM diazoxide for 5 min before reperfusion and otherwise treated the same as group I/R. In groups IPO+5‑hydroxydecanoic acid (5HD), DPO+5HD and I/R+5HD, exposure to 100 µM 5HD (a mitoKATP channel specific blocker) for 5 min before reperfusion as described for groups IPO, DPO and I/R, respectively. In groups IPO+2‑methoxyestradiol (2ME2), DPO+2ME2 and I/R+2ME2, exposure to 2 µM 2ME2 (a HIF‑1α specific blocker) for 10 min before reperfusion as described for groups IPO, DPO and I/R respectively. Cardiac hemodynamics, myocardial injury and the expr...