[Hyperoside alleviates myocardial ischemia-reperfusion injury in rats by activating PKC/mito KATP signaling pathway]

This study investigated the cardioprotective effects of hyperoside against myocardial ischemia-reperfusion injury(MIRI) and its impact on the protein kinase C(PKC)/mitochondrial ATP-sensitive potassium channel(mitoKATP) signaling pathway. A rat MIRI model was established by 30-minute left anterior descending coronary artery ligation followed by 2-hour reperfusion, while an in vitro MIRI model was created using H9c2 cardiomyocytes subjected to 12-hour hypoxia and 4-hour reoxygenation. The models were then treated with hyperoside alone or in combination with PKCα inhibitor bisindolylmaleimide I(BisI), PKCε inhibitor chelerythrine(CHE), or mitoKATP inhibitors 5-hydroxydecanoate(5-HD)/glibenclamide(GB). Myocardial infarct size was assessed by TTC staining; cardiomyocyte apoptosis was detected via TUNEL assay and flow cytometry; serum levels of creatine kinase-MB(CK-MB), superoxide dismutase(SOD), malondialdehyde(MDA), and adenosine triphosphate(ATP) were measured by ELISA; Western blot analyzed protein expression of nuclear factor erythroid 2-related factor 2(Nrf2), PKCε, inward rectifier potassium channel(Kir6.2), and caspase-3 in myocardial tissue and H9c2 cells; calcium ion(Ca~(2+)) levels were detected by immunofluorescence. RESULTS:: demonstrated that hyperoside treatment significantly reduced myocardial infarct area, attenuated tissue edema, fiber disruption, inflammatory infiltration, and decreased apoptosis compared with the model group. Consistent with in vivo findings, hyperoside markedly reduced H9c2 cell apoptosis and Ca~(2+) concentration versus hypoxia/reoxygenation group. Both in vivo and in vitro experiments confirmed that hyperoside decreased MDA content and CK-MB activity, increased SOD activity and ATP levels, upregulated Nrf2, PKCε and Kir6.2 expression, while downregulating caspase-3. These beneficial effects were significantly abolished by co-administration of BisI, CHE, or 5-HD/GB. These findings suggest that hyperoside alleviates MIRI potentially through activating the PKC/mitoKATP signaling pathway.