柠檬苦素调节RIP1/RIP3/MLKL信号通路对心肌梗死大鼠 心肌细胞坏死性凋亡的影响

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【中图分类号】R542.2【文献标志码】A【收稿日期】2023-11-16

【AbstractlObective：Toinvestigateteimpactoflmonin（LI）onteneroticapoptosisofmyocardialcelsinratswithmycardial infarction（MI）by regulating the receptor-interacting protein 1 （RIP1）/receptor-interacting protein 3（RIP3）/mixed-lineage kinase domain-likeprotein（MLKL）signalingpathway.Methods：Atotal of60 Sprague-Dawley rats were randomly divided into shamoperation group（Sham group），MI model group（Model group），lowdose LIM group（LIM-L group，25 mg/kg LIM），high-dose LIM group（LIM-H group，50 mg/kg LIM），and high-dose LIM + RIP1 inhibitor Nec-1 group（LIM-H+Nec-1 group，50 mg/kg LIM+0.6 mg/kg Nec-1）with12rats ineachgroup.AratmodelofMIwas establishedbyligationofthecoronaryartery.Thechangesofcardiacfunction were examinedforeach group；HE staining was used to observe the pathologicalchanges of myocardial tissue;the 2，3，5 -triphenyltetrazolumchloride-Evansblueethodwasusedtomeasure myocardialinfarctarea；theterminaldeoxynucleotidyl transferasemediateddUTPnickendlabeling methodwasused toobservethenecroticapoptosisof myocardialcels；quantitativereal-timePCR andWestern blotwereused to measure theexpresionlevelsofmRNAsand proteinsassociatedwiththeRIP1/RIP3/MLKLsignaling pathwayandtheexpressonofapoptosis-elatedproteins.Results：ComparedwiththeShamgroup，theModelgouphadsignificantreductionsiettlarofrac，fttlarstolicuendxpronlelofellpo（-2） in myocardial tissue（all P<0.001 ）and significant increases in left ventricular end-systolic volume，left ventricular end-diastolic pressure，leftventricularddastolicvoue，ycadialifarctarea，cellaoptosisate，emAandproteiexpressionlelsf RIP1，RIP3，ndLinycaialissu，nderoteiexpresionlvelsofcl-assiatedXproteinndcteate specific proteinase 3 in myocardial tissue（all P<0.001 ），as well as swelling and disordered arrangement of myocardial cells with necrosisandmassiveinflammatorycellinfilrationonHEpathologicalsections.Compared with the Model group，theLIM-Hgroup showed reverse changes in the above indicators（RIP1 mRNA： P =0.002，RIP3 mRNA： P =0.008，and the other indexes P were all < （204号 0.001）withlsfyoaalsopthoicaliuydifmtolilraiopoodt aleviatingthneroticapoptosisofmyocardialcellinats.ConcusionMayallviateteeoticapoptosisofyoadal cells in MI ratsbydownregulating theRIP1/RIP3/MLKL signaling pathway.

【Keywordslimonin;eptornteractingprotein/receptornteractingprotein3/mixedleagekinasedomainlikeproteisigal ing pathway ;myocardial infarction;necrotic apoptosis

心肌梗死（myocardialinfarction，MI）是冠心病中常见的严重类型，在国内外发生率和死亡率均居高不下[1-2]。（剩余12993字）