铁死亡抑制剂通过调控PI3K/AKT/ROS信号通路减轻心肌细胞凋亡的实验研究

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AbstractObjective：Toinvestigatetheeffctofferrostatin-1er-）oncardiomyocyteapotosisincardiovasculardiseasesthugh reactivexygen（ROS）phosphatidylinositol3-kinase（Pl3KproteinKinaseB（AKT）signalingpathwayMethods：RatH9ccardiomcyte wererandomlyaignedtothefolowingexperimentalgroups：thecontrolgroup，thehypoxia/reoxygenation（H/R）group，theH/R十 phosphate-buffered saline（PBS） group，the H/R + low-dose Fer-1 group，the H/R + medium-dose Fer-1 group，and the H/R + high-dose Fer-1 group.The H/R group，H/R + PBS group，H/R + low-dose Fer-1 group，H/R + medium-dose Fer-1 group，and H/R + high-dose Fer-1groupweresubjectedtoH/RinductioninH9c2cels，andthelevelsoflactatedehydrogenase（LDH），oxidativestres，and intracellular ferrous iron （Fe2+ ）were determined.The levels of feroptosis markers glutathione peroxidase 4（GPX4）and acyl-coa synthase 4（ACSL4）weredetected byWestemBlot.H/R-induced H9c2celswere treatedwithFer-1atconcentrationsof1，3，and 12μmol/L ，and celliabityasdetectedeexpressionofl3/AKTsignalinpathwayasdetectedbyealtimefluorescentquantativepolyerase chainreactionandWestemBlotResults：TheresultsshowedthatH/R-inducedH9c2cellviabiltdecreasedwithincreaseofoxidative stress and lactate dehydrogenase content，elevation of Fe2+ and ACSL4 levels，and decrease of GPX4 levels.Fer-1 inhibits H/ R-induced ferroptosisand oxidative stress incardiomyocytes.Theexpression of Pl3K/AKT signaling pathwaydecreased in H/ R-induced H9c2 cells， while Fer-1 treatment increased itsexpression，and the diffrenceswere statistically significant（ P<0.05 ）.Conclusion：Fer-1attenuates H/R-induced iron death in cardiomyocytes by activating the Pl3K/AKT signaling pathway.

Keywordsmyocardialapoptosis;ferroptosis;reactiveygen;posphatidyliositol3-kinase;proteinkinaseB;experimentstudy

心肌梗死（myocardialinfarction，MI）是由于缺氧导致动脉壁形成斑块，导致流向心脏的血流量减少和心肌损伤而引起的一种心脏事件，目前，心肌梗死最有效的干预策略是及时心肌再灌注，包括溶栓治疗和经皮冠状动脉介入治疗，这些干预措施可以迅速恢复缺血心肌的血液循环，缩小心肌梗死面积，防止心力衰竭的发生[1]。（剩余8373字）