Danhong Injection Up-Regulates miR-125b in Endothelial Exosomes and Attenuates Apoptosis in Post-Infarction Myocardium  

作　　者：LI Si-nai LIU Zi-hao ZHOU Ming-xue LIU Wei-hong LAI Xiao-lei LI Ping ZHANG Lei SHANG Ju-ju QIU Sheng-lei LOU Yan TAN Yu-pei XING Wen-long LIU Hong-xu 

机构地区：[1]Department of Cardiology,Beijing Hospital of Traditional Chinese Medicine,Capital Medical University,Beijing(100010),China [2]Beijing Institute of Chinese Medicine,Beijing(100010),China

出　　处：《Chinese Journal of Integrative Medicine》2023年第12期1099-1110,共12页中国结合医学杂志（英文版）

基　　金：Supported by National Natural Science Foundation of China (No.82174106 and No.81703850)。

摘　　要：Objective:To investigate the involvement of endothelial cells(ECs)-derived exosomes in the antiapoptotic effect of Danhong Injection(DHI)and the mechanism of DHI-induced exosomal protection against postinfarction myocardial apoptosis.Methods:A mouse permanent myocardial infarction(MI)model was established,followed by a 14-day daily treatment with DHI,DHI plus GW4869(an exosomal inhibitor),or saline.Phosphatebuffered saline(PBS)-induced ECs-derived exosomes were isolated,analyzed by miRNA microarray and validated by droplet digital polymerase chain reaction(ddP CR).The exosomes induced by DHI(DHI-exo),PBS(PBS-exo),or DHI+GW4869(GW-exo)were isolated and injected into the peri-infarct zone following MI.The protective effects of DHI and DHI-exo on MI hearts were measured by echocardiography,Masson's trichrome staining,and TUNEL apoptosis assay.The Western blotting and quantitative reverse transcription PCR(qR T-PCR)were used to evaluate the expression levels of miR-125b/p53-mediated pathway components,including miR-125b,p53,Bak,Bax,and caspase-3 activities.Results:DHI significantly improved cardiac function and reduced infarct size in MI mice(P<0.01),which was abolished by the GW4869 intervention.DHI promoted the exosomal secretion in ECs(P<0.01).According to the results of exosomal miRNA microarray assay,30 differentially expressed miRNAs in the DHI-exo were identified(28 up-regulated miRNAs and 2 down-regulated miRNAs).Among them,DHI significantly elevated miR-125b level in DHI-exo and DHI-treated ECs,a recognized apoptotic inhibitor impeding p53 signaling(P<0.05).Remarkably,treatment with DHI and DHI-exo attenuated apoptosis,elevated miR-125b expression level,inhibited capsase-3 activity,and down-regulated the expression levels of proapoptotic effectors(p53,Bak,and Bax)in post-MI hearts,whereas these effects were blocked by GW4869(P<0.05 or P<0.01).Conclusion:DHI and DHI-induced exosomes inhibited apoptosis,promoted the miR-125b expression level,and regulated the p53 apoptotic pathway in post-infarction myocardium

关 键 词：EXOSOME Danhong Injection Chinese medicine miR-125b myocardial infarction APOPTOSIS 

分 类 号：R285[医药卫生—中药学]