PDF下载 ( 1346 KB)
Effect of H2S on intracellular Ca2+ concentration in HSCs under H2O2-induced oxidative stress conditions
-
摘要:
目的探讨硫化氢（H2S）对大鼠原代肝星状细胞（HSC）增殖及Ca2+浓度的影响及其作用机制。方法大鼠肝星状原代细胞作为研究对象,将过氧化氢（H2O2）作用于大鼠原代HSC制造肝纤维化的氧化应激模型,用钙离子荧光探针Fluo-3/AM负载细胞,并在此基础上应用不同剂量的NaSH（H2S供体）和KATP通道抑制剂（格列本脲）对各组细胞进行干预,用激光扫描共聚焦显微镜（LSCM）和CCK-8的方法分别检测不同刺激条件对细胞内Ca2+浓度改变及细胞增殖情况的影响。结果低浓度H2S（100μmo/L NaSH）明显降低HSC细胞内Ca2+浓度（P<0.05）,抑制细胞增殖;K离子通道阻断剂——格列本脲可阻断H2S的作用。高浓度H2S（1mmol/L NaSH）使HSC细胞内Ca2+浓度增加,促进细胞增殖。结论低浓度H2S通过激活HSC细胞KATP通道,降低细胞内Ca2+浓度,从而抑制细胞增殖;高浓度H2S使HSC细胞内Ca2+浓度增加,促进细胞增殖。
Abstract:Objective To determine the effects of H2S on rat primary hepatic stellate cell (HSC) proliferation and intracellular calcium (i) concentration and to investigate the underlying mechanisms of these effects.Methods An in vitro model of oxidative stress-induced hepatic fibrosis was established by exposing rat primary HSCs to H2O2.The induced HSCs were loaded with Fluo-3/AM and treated with a KATP channel inhibitor (glyburide) and different concentrations of an H2S donor (NaSH) .The Ca2+ concentration was measured by laser scanning confocal microscopy and the HSC proliferation rate at different H2S concentrations was measured by the CCK-8 assay.Results Exposure to a low concentration of H2S (100 μmo/L NaSH) significantly decreased the i level (P<0.05) and inhibited proliferation of HSCs.KATP channel inhibition blocked the effects of H2S.In contrast, exposure to high concentration of H2S (1 mmo/L NaSH) significantly increased i (P<0.05) and promoted proliferation of HSCs.Conclusion Stimulation of the KATP channel in HSCs by low and high concentrations of H2S produce opposite effects on both i and proliferation.
-
Key words:
- hydrogen sulfide /
- hydrogen peroxide /
- astrocytes /
- microscopy /
- confocal /
- cell proliferation
-
【据Journal of Hepatology 2021年5月报道】题：急性病毒性肝炎的全球负担及其与社会经济发展状态的关系(1990年—2019年)(作者Zeng DY等)
急性病毒性肝炎(AVH)是全球重要的公共卫生健康问题，但由于全球病毒性肝炎防治重心在于后果严重的慢性乙型肝炎(CHB)以及慢性丙型肝炎(CHC)，而关于AVH的研究进展有限。随着最近针对病毒性肝炎的疫苗和治疗方法的进展，需要对AVH的负担进行更深入的了解，从而为全球干预策略提供依据。来自福建医科大学第一附属医院的Zeng等通过全球疾病负担2019数据库(Global Burden of Disease Study 2019)收集4种主要AVH类型的年龄标准化发病率和伤残调整生命年(DALY)率数据，包括A、B、C和E型急性肝炎，并将数据以性别、社会人口指数(SDI)水平、国家和地区进行分层，描述社会经济发展状态(以SDI为代表)与AVH负担的关联性。
2019年，全球4种主要AVH类型的年龄标准化发病率为3615.9(95%CI: 3 360.5~3 888.3)/10万人，年龄标准化DALY率为58.0(47.3~70.0)/10万人。其中，A型急性肝炎全球疾病负担最重。1990年—2019年，因上述4种AVH发病率下降，其年龄标准化DALY率呈现明显下降趋势。上述4种AVH在西非和中非地区及国家中年龄标准化发病率最高。SDI分层结果显示，高水平SDI和中高水平SDI地区的AVH发生率和DALY最低，而中低水平SDI和低水平SDI地区的AVH负担最高。
综上所述，AVH疾病负担与当地社会经济发展水平具有负相关性。因此，2019年全球疾病负担数据有利于决策者实施具有成本效益的AVH干预措施。
摘译自ZENG DY, LI JM, LIN S, et al. Global burden of acute viral hepatitis and its association with socioeconomic development status, 1990-2019[J]. J Hepatol, 2021. DOI: 10.1016/j.jhep.2021.04.035. [Online ahead of print]
(福建医科大学附属第一医院肝病中心 朱月永 报道)
-
[1]Wojtalla A, Herweck F, Granzow M, et al.The endocannabinoid N-arachidonoyl dopamine (NADA) selectively induces oxidative stress-mediated cell death in hepatic stellate cells but not in hepa-tocytes[J].Am J Physiol Gastrointest Liver Physiol, 2012, 302 (8) :873-887. [2]Comporti M, Arezzini B, Signorini C, et al.Oxidative stress, iso-prostanes and hepatic fibrosis[J].Histol Histopathol, 2009, 24 (7) :893-900. [3]杨丹才让, 邓勇, 任利, 等.硫化氢在大鼠肝星状细胞氧应激中对ɑ-SMA与细胞周期影响的实验研究[J].现代生物医学进展, 2010, 12 (10) :2205-2208. [4]王宏宾, 樊海宁, 邓勇, 等.硫化氢对大鼠肝星形细胞增殖和氧应激的影响[J].青海医学院学报, 2008, 29 (4) :228-233. [5]刘懿芷, 邓勇, 秦伟, 等.氧化应激下大鼠肝星状细胞增殖情况及硫化氢含量的变化[J].青海医学院学报, 2009, 30 (3) :145-149. [6]李校天, 杨书良, 王军民, 等.水蛭对Ang一Ⅱ刺激鼠肝星状细胞活化Ca 2+效应的抑制作用[J].中国全科医学, 2006, 9 (6) :472-474. [7]Ryazantseva NV, Novitsky VV, Starikova EG, et al.Role of hydro-gen sulfide in the regulation of cell apoptosis[J].Bull Exp Biol Med, 2011, 151 (6) :702-704. -
下载:
