橙皮素通过调控AMPK/NLRP3通路减轻阿霉素诱导的小鼠心肌毒性

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Abstract： Objective Toverify whether hesperetin （Hes）alleviates doxorubicin （DOX）-induced cardiotoxicity byreducing inflammation viaregulatingthe AMPK/NLRP3 pathway.Methods C57/bl6 miceandH9c2celstreated with DOX to mimic cardiotoxicity were randomlydivided into Sham （orcontrol） group，DOX group，DOX+Hes group，DOX+Hes+compound C （CC，anAMPKinbitorgroup.Cadiacfunctionandmyoadialpathologiesoftemicewereevaatd，andeagesin H9c2cell morphologyand viabilitywere assessed.Lactatedehydrogenase （LDH）activity inmouse myocardialtissuesand H9c2cells was measuredusing ELISA，andH9c2cellapoptosis was detected with TUNELstaining.Inboth H9c2celsand the myocardial tissues of the mice， cellular expression levels of TNF- α ，IL-6 and IL-1β mRNAsand cleaved caspase-3， Bcl2， Bax IL-1β， IL-18，p-AMPK，AMPK，p-mTOR，mTOR，NRP3，ASCandcaspase-1 proteins were detectedusing RT-CRand Westernblotting.ResultsDOXtreatmentcausedcellswelingdecreasedcell viabilityandincreasedLDHactivitynH9c2 cels，resultingalsoinsigiantlyiceasedcellapotosisndceavedcaspase3expresionanddeceasedclBaatioe DOX-treatedmiceshowedobviousmyocardialfiberswelingandinflammatoryinfiltration，decreasedcardiacfunctioand significantlyincreasedmyocardialLDHactivity.InH9c2cels，DOXtreatmentsignificantlyincreasedthemRNAexpesions of TNF- α IL-6and IL- 1β and protein expressions of IL-1β and IL-18，lowered the expressions of p-AMPK and p-mTOR，and increasedtheexpressonsofNRP3，ASCandcaspase-1.HestreatmentobviouslyreducedthesetoxicefectsofDXinH9c2 cels，butitsprotectiveefectswereblockedbyapplicationofcompound C.Conclusion HesreducesDOX-induced cardiotoxicity by inhibiting inflammation via regulating the AMPK/NLRP3 pathway.

Keywords： hesperetin; doxorubicin; AMPK/NLRP3; inflammatory response; H9c2 cells

肿瘤和心血管疾病在全世界范围内发病率和死亡率高。（剩余16013字）