依达拉奉通过调控p38MAPK通路抑制阿霉素的心肌毒性  

Edaravon inhibits the doxorubicin-induced cardiotoxicity by modulating p38 MAPK pathway

作　　者：刘广交[1] 郭润民[2] 徐文明[3] 陈景福[2] 冯鉴强[4] 廖新学[5] 

机构地区：[1]梅州市人民医院心血管内科,广东梅州514000 [2]广东医学院附属医院心内科,广东湛江市524001 [3]中山大学附属第一医院黄埔院区内科,广东广州510080 [4]中山大学中山医学院生理教研室,广东广州510080 [5]中山大学附属第一医院高血压血管病科,广东广州510080

出　　处：《解剖学研究》2013年第5期321-325,共5页Anatomy Research

基　　金：国家自然科学基金(81270296);广东省科技计划项目(2011B080701051;2010B080701105)

摘　　要：目的探讨新型抗氧化剂依达拉奉(edaravone,EDA)能否通过调控p38丝裂原激活蛋白激酶(mitogen-activated protein kinase,MAPK)通路保护H9c2心肌细胞对抗阿霉素(doxorubicin,DOX)引起的损伤。方法应用5μmol/L DOX处理H9c2心肌24 h以建立心肌毒性损伤模型。CCK-8比色法检测细胞存活率;双氯荧光素(DCFH-DA)染色荧光显微镜照像测定细胞内活性氧(reactive oxygen species,ROX)水平;罗丹明123(rh123)染色荧光显微镜照像检测线粒体膜电位(mitochondrial membrane potential,MMP);Western blot法测定p38MAPK蛋白表达水平。结果在15~60 min的时间范围内,5μmol/L DOX呈时间依赖性地上调磷酸化(phosphorylated,P)p38MAPK表达。在DOX处理心肌细胞前,应用40μmol/L EDA预处理60 min不仅能抑制DOX对p-p38MAPK表达的上调作用,也能抑制DOX引起的心肌细胞损伤,使细胞存活率升高、胞内ROS生成减少及MMP丢失减少。另方面,应用了3μmol/L SB203580(p38MAPK抑制剂)预处理60 min也产生类似于上述的EDA对抗DOX心肌毒性的作用。结论 EDA可通过抑制p38MAPK通路保护H9c2心肌细胞对抗DOX引起的损伤。Objective To explore whether edaravon（EDA）, a novel antioxidant, can protect H9c2 cardiac cells against the doxorubicin-induced injury by modulating p38 mitogen-activated protein kinase （MAPK） pathway. Methods H9c2 cardiac cells were treated with 5 μmol/L doxorubicin （DOX） to establish a model of cardiotoxicity injury. Cell viability was detected by cell counter kit （CCK-8）. Intracellular level of reactive oxygen species （ROS） was tested by DCFH-DA staining and photofluorography ; Mitochondrial membrane potential （MMP） was examined by rhodamine 123 （RH123） staining and photofluorography. The expres- sion level of p38 MAPK protein was observed by Western blot assay. Results Ranging from 15 min to 60 min, DOX at 5 I^mol/L time-dependently upregulated the expression of phosphorylated （p） p38 MAPK in H9c2 cardiac cells. Preteeatment of H9c2 cells with 40 Ixmol/L for 60 min before exposure to 5 p, mol/L DOX inhibited not only the DOX-induced upregulation of p-p38 MAPK expression, but also the DOX-induced cardiomyoeyte injuries, as evidenced by an increase in cell viability, and decreases in intra- cellular ROS genernation as well as MMP loss. Moreover, pretreatment with 3 p^mol/L SB 203580, an inhibitor of p38 MAPK, for 60 min prior to exposure to DOX also had a similar protective effect against the DOX-induced carotoxieity as EDA one mentioned above. Conclusion EDA can protect against the DOX-induced injury by modulating p38 MAPK pathway in H9e2 cardiac cells.

关 键 词：依达拉奉 P38丝裂原激活蛋白激酶 阿霉素 活性氧 心肌毒性 

分 类 号：R965[医药卫生—药理学]