右美托咪定通过核因子κB缓解阿霉素诱导的心肌损伤  

Dexmedetomidine attenuates doxorubicin-induced myocardial injury through nuclear factorκB

作　　者：曹雪峰[1] 赵亮[2] 刘旭东[3] 刘汉成[4] 董天鑫[1] 罗艾静 李艳[1] CAO Xuefeng;ZHAO Liang;LIU Xudong;LIU Hancheng;DONG Tianxin;LUO Aijing;LI Yan(Department of Anesthesiology,Affiliated Hospital of Chengde Medical College,Hebei Key Laboratory of Panvascular Disease,Chengde 067000,China;Department of Pharmacology,Chengde Medical College,Hebei Key Laboratory of Nerve Injury and Repair,Chengde 067000,China;Department of Anesthesiology and Pain,Chengde Central Hospital,Chengde 067000,China;Department of Breast Surgery,Affiliated Hospital of Chengde Medical College,Chengde 067000,China)

机构地区：[1]承德医学院附属医院麻醉科,河北省泛血管疾病重点实验室,河北承德067000 [2]承德医学院药理教研室,河北省神经损伤与修复重点实验室,河北承德067000 [3]承德市中心医院麻醉疼痛科,河北承德067000 [4]承德医学院附属医院乳腺外科,河北承德067000

出　　处：《中国医科大学学报》2025年第4期289-294,共6页Journal of China Medical University

基　　金：国家自然科学基金(81700310);河北省重点研发计划(22377746D);河北省中医药管理局科研计划(2024119);河北省泛血管疾病重点实验室开放课题(FXGJBKKFT2403)。

摘　　要：目的探讨右美托咪定(Dex)通过调节核因子κB(NF-κB)缓解阿霉素(Adr)诱导的心肌损伤的机制。方法将SD大鼠分为control组、Adr组、Adr+Dex组,取心肌织织进行HE染色、免疫组织化学染色,实时定量PCR、Western blotting检测。培养大鼠原代心肌细胞及乳腺癌细胞系MDA-MB-23、肺癌细胞系H226、胃癌细胞系AGS和膀胱癌细胞系5637,并分为control组、Adr组、Adr+Dex组、Dex组、Adr+Dex+NF-kBi组,进行CCK-8实验、免疫荧光染色、活性氧(ROS)含量检测。结果Adr组大鼠心肌排列紊乱,心肌细胞活性下降,线粒体膜电位降低,ROS生成增加,NF-κB mRNA和蛋白表达显著减少。Adr+Dex组心肌细胞形态改善,细胞活性增加,线粒体膜电位升高,ROS生成减少,Adr+Dex组NF-κB表达显著增加。Adr+Dex+NF-kBi组线粒体膜电位降低,且ROS生成增加。Adr组肿瘤细胞活性降低,与Adr+Dex组比较无统计学差异。结论Dex不影响Adr的化疗效果,可能通过调节NF-κB改善心肌线粒体膜电位及减少ROS生成,减轻Adr诱导的心肌损伤。Objective To explore the mechanism through which dexmedetomidine(Dex)alleviates doxorubicin(Adr)-induced myocardial injury via regulating nuclear factorκB(NF-κB)expression.Methods Sprague-Dawley rats were divided into control,Adr,and Adr+Dex groups.Theirs hearts were harvested for hematoxylin and eosin(HE)staining,immunohistochemical staining,real-time polymerase chain reaction(PCR),and Western blotting anlyses.The rat primary cardiomyocytes,breast cancer cell line MDA-MB-23,lung cancer cell line H226,gastric cancer cell line AGS,and bladder cancer cell line 5637 were cultured and divided into control,Adr,Adr+Dex,Dex,and Adr+Dex+NF-kBi groups.CCK-8 and immunofluorescence staining were performed to detect the reactive oxygen species(ROS)contents.Results The myocardial arrangement of the rats in the Adr group was disordered,myocardial cell activity was lower,the mitochondrial membrane potential was lower,ROS production was higher,and NF-κB mRNA and protein contents were substantially lower than those in the control group.The cardiomyocyte morphology was improved,cell activity was higher,mitochondrial membrane potential was increased,ROS production decreased,and NF-κB expression significantly increased in the Adr+Dex group compared with those in the control group.The mitochondrial membrane potential in the Adr+Dex+NF-kBi group was lower,and ROS generation was increased compared with the control group.The activity of the tumor cells in the Adr group was lower,and no statistically significant differences were found compared with that in the Adr+Dex group.Conclusion Treatment with Dex may not affect the chemotherapeutic effects of Adr.Dex administration may increase the myocardial mitochondrial membrane potential and reduce ROS generation by regulating NF-κB levels,thereby reducing Adr-induced myocardial damage.

关 键 词：右美托咪定 阿霉素 核因子ΚB 心肌损伤 

分 类 号：R972[医药卫生—药品]