科罗索酸对阿霉素诱导的H9c2心肌细胞的保护作用  

Protective effects of corosolic acid on doxorubicin-induced cardiotoxicity in H9c2 cardiomyocytes

作　　者：贾享 贺武斌 杨秋实 黄建华 JIA Xiang;HE Wu-bin;YANG Qiu-shi;HUANG Jian-hua(The First Hospital Affiliated to Jinzhou Medical University,Jinzhou 121000,China)

机构地区：[1]锦州医科大学附属第一医院,辽宁锦州121000

出　　处：《中成药》2024年第2期451-457,共7页Chinese Traditional Patent Medicine

基　　金：辽宁省新辽英才科技创新领军人才项目(XLYC1802113)。

摘　　要：目的探讨科罗索酸对阿霉素诱导的H9c2心肌细胞的保护作用及其机制。方法筛选并确定科罗索酸浓度,建立1μmol/L阿霉素诱导H9c2心肌细胞损伤模型,加入不同浓度科罗索酸共同处理24 h,MTT法检测细胞活性,Hoechst 33342染色法检测细胞核凋亡形态,Annexin V-FITC/PI双染法检测细胞凋亡率,DCFH-DA探针检测细胞内ROS水平,铁离子比色法检测细胞内铁水平,Western blot法检测细胞Bax、Bcl-2、cleaved-caspase3、Nrf2、GPX4及Ptgs2蛋白表达。结果科罗索酸能够提高阿霉素诱导的H9c2心肌细胞的活力及存活率(P<0.05),降低ROS、Fe^(2+)水平及凋亡率(P<0.05);上调Bcl-2、Nrf2及GPX4蛋白表达(P<0.05),下调Bax、cleaved-caspase3及Ptgs2蛋白表达(P<0.05)。结论科罗索酸能抑制阿霉素诱导的H9c2心肌细胞ROS水平及细胞凋亡,并激活Nrf2/GPX4通路抑制细胞铁死亡。AIM To investigate the protective effects and the mechanism of corosolic acid on doxorubicin-induced cardiotoxicity in H9c2 cardiomyocytes.METHODS To screen and determine the effective concentration of corosolic acid,the injury models of H9c2 cardiomyocytes established by 1μmol/L doxorubicin were exposed to 24 h different concentrations of corosolic acid,followed by detections of their cell activity by MTT method;their cell apoptosis morphology by Hoechst 33342 staining method;their cell apoptosis rate by Annexin V-FITC/PI double staining method;their intracellular ROS level by DCFH-DA probe;their intracellular iron level by iron ion colorimetry;and their protein expressions of Bax,Bcl-2,cleaved-caspase3,Nrf2,GPX4 and Ptgs2 by Western blot.RESULTS Upon the doxorubicin-induced injury models of H9c2 cardiomyocytes,corosolic acid improved their viability and survival rate(P<0.05),decreased their levels of ROS and Fe^(2+)and the apoptosis rate(P<0.05),up-regulated the protein expressions of Bcl-2,Nrf2 and GPX4(P<0.05),and down-regulated the protein expressions of Bax,cleved-caspase 3 and Ptgs2(P<0.05).CONCLUSION Corosolic acid can inhibit the ROS level and apoptosis of doxorubicin-induced injury models of H9c2 cardiomyocytes,and the iron death as well via activating Nrf2/GPX4 pathway.

关 键 词：科罗索酸 阿霉素心肌损伤 凋亡 铁死亡 活性氧 Nrf2/GPX4通路 

分 类 号：R285.5[医药卫生—中药学]