鐵死亡抑制劑通過(guò)調(diào)控PI3K/AKT/ROS信號(hào)通路減輕心肌細(xì)胞凋亡的實(shí)驗(yàn)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）是由于缺氧導(dǎo)致動(dòng)脈壁形成斑塊，導(dǎo)致流向心臟的血流量減少和心肌損傷而引起的一種心臟事件，目前，心肌梗死最有效的干預(yù)策略是及時(shí)心肌再灌注，包括溶栓治療和經(jīng)皮冠狀動(dòng)脈介入治療，這些干預(yù)措施可以迅速恢復(fù)缺血心肌的血液循環(huán)，縮小心肌梗死面積，防止心力衰竭的發(fā)生[1]。（剩余8373字）