杜拉鲁肽对阿霉素诱导心肌细胞损伤的作用及机制  

Effect and mechanism of dulaglutide upon doxorubicin-induced cell injuryof cardiomyocytes

作　　者：方文熙 谢赛阳 邓伟[1] FANG Wen-Xi;XIE Sai-Yang;DENG Wei(Department of Cardiology,Renmin Hospital of Wuhan University&Hubei key Laboratory of Metabolic and Chronic Disea-ses,Wuhan 430061,Hubei,China)

机构地区：[1]武汉大学人民医院心血管内科代谢与相关慢病湖北重点实验室,湖北武汉430060

出　　处：《中国老年学杂志》2024年第15期3696-3700,共5页Chinese Journal of Gerontology

基　　金：国家自然科学基金(82170245,82370284)。

摘　　要：目的探讨杜拉鲁肽对阿霉素所致的心肌细胞损伤的作用及其机制。方法用杜拉鲁肽和阿霉素共同孵育心肌细胞H9C224 h后并用CCK-8法检测H9C2心肌细胞活性,采用TUNEL染色观察H9C2细胞凋亡,二氯荧光素双乙酸盐(DCFH-DA)荧光探针技术检测活性氧(ROS)水平,实时荧光定量聚合酶链反应(RT-qPCR)检测H9C2心肌细胞中凋亡相关蛋白B细胞淋巴瘤(Bcl)-2和Bcl-2相关X蛋白(Bax)mRNA表达及氧化应激相关因子醌氧化还原酶(NQO)1、谷胱甘肽过氧化物酶(GPX)和还原型烟酰胺腺嘌呤二核苷酸磷酸氧化酶(NOX)4 mRNA表达,Western印迹检测H9C2细胞凋亡和氧化应激相关蛋白及相关信号通路蛋白表达。结果杜拉鲁肽干预上调心肌细胞Bcl-2 mRNA表达,降低半胱氨酸天冬氨酸蛋白水解酶(caspase)-3蛋白表达,减少阿霉素诱导的ROS生成,促进NQO1和GPX mRNA表达,降低NOX4 mRNA表达,激活心肌细胞内磷脂酰肌醇-3激酶(PI3K)/蛋白激酶B(AKT)/c-Jun氨基末端转移酶(JNK)信号通路,差异均有统计学意义(P<0.05)。结论杜拉鲁肽通过活化PI3K/AKT/JNK信号通路改善阿霉素诱导的心肌细胞凋亡和氧化应激,减轻心肌细胞损伤。Objective To investigate the effect and mechanism of dulaglutide on myocardial cytotoxic injury induced by doxo-rubicin.Methods After co-incubating H9C2 cardiomyocytes with dulaglutide and doxorubicin for 24 h,the activity of H9C2 cardio-myocytes was detected by CCK8,H9C2 cardiomyocytes apoptotic was observed by TUNEL staining,reactive oxygen species(ROS)level was detected by 2′,7′-dichlorodihydrofluorescein diacetate(DCFH-DA)fluorescent probe technology,the apoptosis related pro-teins including B-cell lymphoma(Bcl)-2 and Bcl-2 associated X protein(Bax)mRNA expressions and oxidative stress related factors including the mRNA expressions of antioxidant factor recombinant NADH dehydrogenase,quinone(NQO)1,glutathione peroxidase(GPX)and the pro-oxidative factor recombinant NADPH oxidase(NOX)4 mRNA expressions in H9C2 cardiomyocytes were detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR).The expressions of apoptosis and oxidative stress related proteins and related signaling pathway proteins in H9C2 cells were detected by Western blot.Results Duraglutide intervention could upregulate the expression level of Bcl-2 mRNA in cardiomyocytes,and decrease the protein expression of caspase-3,doxorubicin-in-duced ROS production,promote the mRNA expressions of NQO1 and GPX,reduce the expression of NOX4 mRNA,activate phosphati-dylinositol 3-kinase(PI3K)/protein kinase B(AKT)/c-Jun N-terminal kinase(JNK)signaling pathways in cardiomyocytes,the differ-ences were all statistically significant(P<0.05).Conclusions Duraglutide could improve adriamycin-induced apoptosis and oxidative stress of cardiomyocytes by activating PI3K/AKT/JNK signaling pathway,and alleviate myocardial cell damage.

关 键 词：杜拉鲁肽 阿霉素 心肌细胞H9C2 细胞凋亡 

分 类 号：R542.2[医药卫生—心血管疾病]