肉桂酸通过抑制TLR4减轻阿霉素诱导的小鼠心肌损伤铁死亡的发生

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Abstract： Objective Toexplore the mechanism ofcinnamicacid （CA）for improving doxorubicin-induced myocardial injury （DIC）in mice.Methods Network pharmacologyanalysis wasused toobtain the keytargetsofCAandDIC.MaleC57BL/6J micewere randomized intoSham，DOX，CA （25，50 and 100mg/kg/+DOX， and CA+Ferrostatin-1+DOX groups， and their myocardial functionandpathology wereexaminedbyechocardiographyandHEstaining.SerumlevelsofCK-MB，LDH， MDA，IL-6，F-andmocardialOlevelereetectedandtheexpressionlevelsofR4andferrotosispathay proteinsinmyocardialtisseweredetectedbyWesternbloting.Culturedmurinecardiomyocytes（HL-1cels）withorwithout transfectionwithasmallinterferingRNAtargetingTLR4（si-LR4）weretreatedwithDOXorErastinandthecelllarROS contentwasmeasuredbyDCFH-DAstaining;theexpresionlevelofGPX4wasdetectedusingimmunofluorescencestaining. Results Network pharmacology analysis suggested that CAmay improve DICthrough TLR4 signaling.DOX treatmentcaused obviousmyocarialinjurynice，ichoedignicantlreasedsumlevelsofCK-，H，A，6 α and myocardialROSlevel with decreasedmyocardial levelsof SLC7A11andGPX4 proteins and increased levelsof TLR4and PTGS2 proteins.Allthesechanges inthemousemodels weresignificantlyaleviatedbytreatment withCA，andthemice receivingCAorferostatin-1treatmentexhibitedincreasedmyocardialexpresionsofSLC7A11andGPX4proteinsand loweredexpressonsofTLR4andPTGS2proteins.InculturedHL-1cells，treatmentwithDOXandErastinbothobviously increasedintracellarROSlevelanddecreasedcellarGPX4expressionlevel，andtesechangeswerestronglyttedby TLR4 interference.ConclusionCA，asapotentherbalmonomer，canefectivelyallviateDICinmicebyinibitingTR4- mediated ferroptosis.

eywords： cinnamicacid;doxorubicin-inducedmyocardialinjury;ferroptosis;Tol-likereceptor 4; network pharmacolo

阿霉素（DOX）作为临床上常用的蒽环类抗生素，用于各种类型癌症（如乳腺癌、肺癌、卵巢癌和甲状腺癌）的治疗1。（剩余18058字）