Protective effects of hydrogen sulfide on oxidative stress and fibrosis in hepatic stellate cells
Protective effects of hydrogen sulfide on oxidative stress and fibrosis in hepatic stellate cells
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DOI：
10.3892/mmr.2012.1153
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发表时间：
2013-01-01
影响因子：
3.4
通讯作者：
Deng, Yong
中科院分区：
文献类型：
--
作者：
Fan, Hai-Ning;Wang, Hai-Jiu;Deng, Yong
在肝纤维化中，肝星状细胞（HSC）被激活并转变为肌纤维母细胞样细胞，其特征在于增殖和细胞外基质（ECM）合成增加。在这项研究中，我们研究了硫化氢（H2S）对肝纤维化的调节作用。我们检测了H2S释放分子NaHS处理的次氮基三乙酸铁（Fe-NTA）激活的HSC的增殖、细胞周期进程、凋亡、细胞内活性氧（ROS）和游离钙水平。我们还评估了NaHS对四氯化碳（CCl 4）诱导的肝纤维化大鼠纤维化和ECM合成的影响。MTT法显示NaHS（500 μ mol/l）呈剂量依赖性抑制Fe-NTA诱导的HSC-T6细胞增殖。NaHS诱导Fe-NTA处理的HSC-T6细胞发生G1期阻滞和凋亡。此外，NaHS还能降低Fe-NTA处理HSC-T6细胞后1、3和6 h细胞内ROS水平，降低3和6 h细胞内游离钙水平。H2S给药减轻CCl 4诱导的肝纤维化大鼠的肝纤维化和I型胶原蛋白表达。总之，外源性H2S抑制增殖，诱导活化的HSC细胞周期阻滞和凋亡，并减弱CCl 4诱导的肝纤维化和ECM表达。
In hepatic fibrosis, hepatic stellate cells (HSCs) are activated and change into myofibroblast-like cells which are characterized by increased proliferation and extracellular matrix (ECM) synthesis. In this study, we investigated the regulatory effects of hydrogen sulfide (H2S) on hepatic fibrosis. We detected the proliferation, cell cycle progression, apoptosis, intracellular reactive oxygen species (ROS) and free calcium levels in ferric nitrilotriacetate (Fe-NTA)-activated HSCs treated with sodium hydrogen sulphide (NaHS), an H2S-releasing molecule. We also evaluated the effects of NaHS on fibrosis and ECM synthesis in rats with hepatic fibrosis induced by carbon tetrachloride (CCl4). MTT assay revealed that NaHS (500 mu mol/l) suppressed the Fe-NTA-induced proliferation of HSC-T6 cells in a dose-dependent manner. NaHS induced G1 phase cell cycle arrest and apoptosis in the Fe-NTA-treated HSC-T6 cells. Furthermore, in the Fe-NTA-treated HSC-T6 cells, NaHS reduced intracellular levels of ROS at 1,3 and 6 h and reduced intracellular free calcium levels at 3 and 6 h. H2S administration attenuated hepatic fibrosis and collagen I protein expression in the rats with CCl4-induced hepatic fibrosis. In conclusion, exogenous H2S inhibits proliferation and induces cell cycle arrest and apoptosis in activated HSCs and attenuates CCl4-induced hepatic fibrosis and ECM expression.