硫化氢对大鼠心脏成纤维细胞增殖的抑制作用  

Inhibitory effect of hydrogen sulfide on cardiac fibroblast proliferation

作　　者：刘俊[1] 郝丹丹[1] 朱依纯[1] 

机构地区：[1]复旦大学上海医学院生理学与病理生理学系,上海200032

出　　处：《生理学报》2011年第4期353-358,共6页Acta Physiologica Sinica

基　　金：supported by the National Natural Science Foundation of China(No.30470628)

摘　　要：本文旨在研究硫化氢(hydrogen sulfide,H2S)对大鼠心脏成纤维细胞增殖的抑制作用。以原代培养新生大鼠心脏成纤维细胞(neonatal ratcardiac fibroblasts,NRCFs)为研究对象,用不同浓度血管紧张素II(angiotensin Ⅱ,Ang Ⅱ)或胎牛血清(fetalbovineserum,FBS)刺激NRCFs,建立NRCFs增殖模型。不同浓度硫氢化钠(NaHS,H2S的供体)处理该NRCFs增殖模型后,采用5’-溴-2’-脱氧尿嘧啶(5’-bromo-2’-deoxyuridine,BrdU)掺入法检测NRCFs增殖情况,用2’,7’-二氯荧光素乙酰乙酸盐(2’,7’-di-chlorofluorescein diacetate,DCFH-DA)荧光探针法检测细胞活性氧类(reactive oxygen species,ROS)水平。结果显示,较低浓度的NaHS(1×105mol/L)能促进FBS(2%、10%)对NRCFs的诱导增殖作用,但对Ang Ⅱ(1×107mol/L)所引起的NRCFs增殖的作用不明显,而较高浓度NaHS(5×105、1×104mol/L)则显著抑制10%FBS和Ang Ⅱ(1×107mol/L)对NRCFs的诱导增殖作用;1×104mol/LNaHS可显著降低Ang Ⅱ(1×107mol/L)诱导升高的细胞内ROS水平。以上结果表明,H2S在一定浓度范围内具有抑制NRCFs增殖的作用,其机制可能与H2S降低细胞内ROS有关。The aim of the present study was to investigate the role of hydrogen sulfide （H 2 S） in the proliferation of neonatal rat cardiac fibroblasts （NRCFs）. Proliferation of NRCFs was induced by the presence of fetal bovine serum （FBS） or angiotensin Ⅱ （Ang Ⅱ） at various concentrations. The concentration-dependent effect of NaHS （donor of H 2 S） on NRCFs proliferation was examined. NRCFs proliferation was assessed by 5’-bromo-2’-deoxyuridine （BrdU） incorporation method. Reactive oxygen species （ROS） level was measured using the dye probe, 2’, 7’-dichlorofluorescein diacetate （DCFH-DA）. The results showed that FBS- or Ang Ⅱ-induced NRCFs proliferations were inhibited with the treatment of relatively high concentrations of NaHS （5 × 10 5 mol/L, 1 × 10 4 mol/L）, but FBS-induced proliferation was increased by low concentration of NaHS （1 × 10 5 mol/L）. Two or 6 h of Ang Ⅱ （1 × 10 7 mol/L） treatment caused an increase of ROS level in NRCFs, while this increase was inhibited with NaHS （1 × 10 4 mol/L） treatment. These results suggest that H 2 S is an inhibitor of cardiac fibroblast at a certain concentration range. This inhibitory effect may be mediated by a reduction in intracellular ROS production.

关 键 词：硫化氢 大鼠 心脏成纤维细胞 血管紧张素Ⅱ 

分 类 号：R363[医药卫生—病理学]