摘要
目的:探讨囊性纤维化跨膜传导调节因子(CFTR)氯通道在硫化氢(H2S)诱导的心肌保护及细胞增殖中的作用。方法:应用氯化钴(CoCl2)在大鼠H9c2心肌细胞建立化学性缺氧损伤心肌细胞实验模型;CCK-8试剂盒检测心肌细胞存活率;Hoechst 33342核染色法检测心肌细胞凋亡。结果:在400-2 000μmol/L浓度范围内,CoCl2呈剂量依赖性地抑制H9c2心肌细胞的存活率,600μmol/L CoCl2能诱导H9c2心肌细胞产生明显的凋亡;在100-800μmol/L浓度范围内,硫氢化钠(NaHS)呈剂量依赖性地促进H9c2心肌细胞增殖;NaHS能保护H9c2心肌细胞对抗CoCl2引起的细胞损伤作用,使细胞存活率升高,凋亡率降低;100μmol/L CFTR氯通道拮抗剂5-硝基-2-(3-苯丙胺)-苯甲酸(NPPB)能明显地阻断NaHS对CoCl2的细胞毒性的抑制作用,但不能阻断NaHS抗心肌细胞凋亡作用及促进心肌细胞增殖作用。结论:CFTR氯通道可能参与H2S的抗CoCl2引起的心肌细胞毒性作用。
AIM： To explore the roles of cystic fibrosis transmembrane conductance regulator （CFTR） Cl- channels in hydrogen sulfide （H2S） -induced cardioprotection and cell proliferation in H9c2 cells. METHODS： Cobalt chloride （CoCl2 ） was used to set up the chemical hypoxiainduced injury model in H9c2 cells. Myocardial cell viability was detected by the CCK- 8 assay kit. Apoptotic changes in H9c2 cells were observed by using Hoechst 33342 staining and photofluorography. RESULTS ： At the concentrations from 400 to 2 000 μ mol/L, CoCl2 dose - dependently inhibited cell viability in H9c2 cells. CoCl2 at concentration of 600 μmol/L significantly induced H9c2 cell apoptosis. Sodium hydrosulfide （NariS） at concentrations from 100 to 400 μmol/L dose - dependently enhanced proliferation in H9c2 cells. NariS protected H9c2 cells against CoCl2 - induced injury, including an increase in cell viability and a decrease in percentage of apoptosis. 5 - nitro -2 - （3 - phenylpropylamino） - benzoic acid （ NPPB, 100 μmol/L）, an inhibitor of CFTR Cl- channels alone did not damaged H9c2 cells, but considerably blocked the inhibitory effect of NariS on CoCl2 cytotoxicity. However, NPPB did not antagonize the NariS - induced antiapoptotic effect and cell proliferation in H9c2 cells. CONCLU- SION： CFTR Cl - channels may be involved in the inhibitory effect of H2S on CoCl2 - induced cytotoxieity in H9c2 cells.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2009年第6期1070-1075,共6页
Chinese Journal of Pathophysiology
基金
广东省科技计划资助项目(No.2006B60501024No.2007B080701030)
关键词
氯通道
硫化氢
心肌保护
细胞增殖
氯化钴
Chloride channels
Hydrogen sulfide
Cardioprotection
Cell proliferation
Cobalt chloride
