纳米阿霉素通过诱导自噬减弱心肌毒性的作用机制  

Mechanism of Nano-doxorubicin Attenuating Cardiotoxicity by Inducing Autophagy

作　　者：韩宁 刘斌 彭兴春 李留根 徐华珍 陈效[2] 李童斐 HAN Ning;LIU Bin;PENG Xing-chun;LI Liu-gen;XU Hua-zhen;CHEN Xiao;LI Tong-fei(Department of Pharmacology,School of Basic Medical Sciences,Hubei University of Medicine,Shiyan,Hubei 442000;Department of Pharmacology,School of Basic Medical Sciences,Wuhan University,Wuhan,Hubei 430000,China)

机构地区：[1]湖北医药学院基础医学院药理学教研室,湖北十堰442000 [2]武汉大学基础医学院药理学教研室,湖北武汉430000

出　　处：《湖北医药学院学报》2022年第3期219-223,228,F0002,共7页Journal of Hubei University of Medicine

基　　金：湖北省科技厅项目(2020CFB152);湖北医药学院人才启动金项目(2020QDJZR002,2019QDJZR02);湖北医药学院研究生创新项目(YC2021016);国家级大学生创新创业训练项目(202110929010,202113249001)。

摘　　要：目的:验证功能化纳米载体装载阿霉素(Nano-DOX)能否通过诱导自噬减弱阿霉素(DOX)的心肌毒性。方法:利用倒置荧光显微镜、CCK-8及流式细胞术检测Nano-DOX被心肌细胞摄取的情况及其对心肌细胞活力的影响;利用蛋白质免疫印迹法检测Nano-DOX对心肌细胞自噬的影响。结果:Nano-DOX被摄取后主要分布于心肌细胞的细胞质且能使心肌细胞保持较高活力。Nano-DOX诱导心肌细胞凋亡弱于DOX,而诱导心肌细胞自噬的作用明显较强。自噬抑制剂能够显著削弱Nano-DOX对心肌细胞的保护作用。结论:本研究的结果表明Nano-DOX可通过诱导心肌细胞自噬减弱化疗药物DOX对心肌的毒性。该策略为减少DOX在临床应用上的限制提供了新的思路。Objective To investigate whether the functional nanocarrier-modified doxorubicin(Nano-DOX)could attenuate cardiotoxicity by inducing autophagy.Methods Inverted fluorescence microscope,CCK-8 and flow cytometry were used to detect the uptake of Nano-DOX by cardiomyocytes and its effect on cardiomyocyte viability.Western blot was used to detect the effect of Nano-DOX on cardiomyocyte autophagy.Results Nano-DOX was mainly distributed in the cytoplasm of cardiomyocytes after being taken up and can keep cardiomyocytes at a high level of viability.Nano-DOX-induced cardiomyocyte apoptosis was weaker than DOX,while the induction of cardiomyocyte autophagy was significantly stronger.Autophagy inhibitors could significantly attenuate the protective effect of Nano-DOX on cardiomyocytes.Conclusion The present study demonstrates that Nano-DOX can attenuate the cardiotoxicity of chemotherapeutic DOX by inducing autophagy in cardiomyocytes.This strategy provides a novel approach for eliminating the limitations of DOX in clinical applications.

关 键 词：心肌毒性 多柔比星(阿霉素) 自噬 化疗 纳米药物 

分 类 号：R96[医药卫生—药理学]