硫化氢保护衣霉素诱导的人心脏成纤维细胞应激损伤  

Hydrogen Sulfide Protects Human Cardiac Fibroblasts Against Tunicamycin-induced Stress Damage

作　　者：张蕾 武文艺 吴三五 李冬 张友恩 ZHANG Lei;WU Wen-yi;WU San-wu;LI Dong;ZHANG You-en(Institute of Clinical Medicine,Renmin Hospital,Hubei University of Medicine,Shiyan,Hubei 442000,China;Arteriosclerosis Cardiovascular Disease(ASCVD)Clinical Medical Research Center of Hubei Province,Renmin Hospital,Hubei University of Medicine,Shiyan,Hubei 442000,China;Shiyan Key Laborato-ry of Arteriosclerosis Diseases Research,Renmin Hospital,Hubei University of Medicine,Shiyan,Hubei 442000,China;Department of Cardiology,Renmin Hospital,Hubei University of Medicine,Shiyan,Hubei 442000,China)

机构地区：[1]湖北医药学院附属人民医院临床医学研究所,湖北十堰442000 [2]湖北医药学院附属人民医院动脉粥样硬化性心血管疾病(ASCVD)临床医学研究中心,湖北十堰442000 [3]湖北医药学院附属人民医院动脉粥样硬化疾病研究十堰市重点实验室,湖北十堰442000 [4]湖北医药学院附属人民医院心血管内科,湖北十堰442000

出　　处：《湖北医药学院学报》2024年第3期242-246,F0002,F0003,共7页Journal of Hubei University of Medicine

基　　金：国家自然科学基金青年科学基金项目(81500237);湖北省科技厅重点研发计划(2022BCE007);湖北医药学院药护学院教研项目(YHJ2021037)。

摘　　要：目的:观察硫化氢(hydrogen sulfide,H2S)对内质网应激细胞损伤的保护作用,并探讨Caspase 3/Bax/Bcl-2信号通路机制。方法:人心脏成纤维细胞(human cardiac fibroblasts,HCF)随机分为对照组(Control)、硫氢化钠组(NaHS)、衣霉素组(Tunicamycin)、NaHS+Tunicamycin组。DHE染色检测ROS水平;JC-1检测线粒体膜电位;LysoTracker Deep Red检测溶酶体活性;Western blot分析检测Caspase 3、Bax和Bcl-2的表达;Annexin V凋亡检测试剂盒检测细胞凋亡。结果:与Control组比较,Tunicamycin组ROS水平、溶酶体活性、细胞凋亡均升高,线粒体膜电位降低,Caspase 3、Bax表达增强,Bcl-2表达减弱。与Tunicamycin组比较,NaHS干预可以降低细胞ROS生成、溶酶体活性、细胞凋亡,抑制膜电位丢失,Caspase 3、Bax表达减弱,Bcl-2表达增强。结论:H2S对衣霉素诱导的细胞损伤具有保护作用,其作用机制与保护线粒体功能,抑制Caspase 3/Bax/Bcl-2凋亡信号通路有关。Objective To explore the protective effects of hydrogen sulfide(H2S)against endoplasmic reticulum stress-in⁃duced cellular damage and to investigate the mechanisms involving the Caspase3/Bax/Bcl-2 signaling pathway.Methods Human cardiac fibroblasts(HCFs)were randomly divided into four groups:control,sodium hydrosulfide(NaHS),tunica⁃mycin,and NaHS+tunicamycin.Reactive oxygen species(ROS)levels were detected with DHE staining.Mitochondrial membrane potential was measured using the JC-1 fluorescent probe.Lysosomal activity was assessed using LysoTracker Deep Red.The expressions of Caspase 3,Bax,and Bcl-2 were determined by Western blot,and apoptosis was assessed by Annexin V.Results Compared with the control group,the tunicamycin group had increased ROS levels,lysosomal activity,and cell apoptosis,alongside decreased mitochondrial membrane potential,enhanced expressions of Caspase 3 and Bax,and lowered expression of Bcl-2.Compared with the tunicamycin group,NaHS in the NaHS+tunicamycin group reduced cellular ROS production,lysosomal activity,cell apoptosis,and prevented loss of membrane potential,with decreased ex⁃pressions of Caspase 3 and Bax while increased expression of Bcl-2.Conclusion H2S provides protection against tunicamy⁃cin-induced cellular damage in human cardiac fibroblasts.Its mechanism is associated with preserving mitochondrial func⁃tion and inhibiting the Caspase 3/Bax/Bcl-2 signaling pathway.

关 键 词：硫化氢 内质网应激 线粒体 Caspase 3/Bax/Bcl-2 细胞凋亡 

分 类 号：R54[医药卫生—心血管疾病]