Department of Anesthesiology and Critical Care Medicine, University Medical Center, Freiburg, Germany.
Pancreas. 2012 Jan;41(1):74-83. doi: 10.1097/MPA.0b013e318223645b.
Pancreatic stellate cells (PSCs) play a crucial role during pancreatic fibrosis development. Hydrogen sulfide (H2S) is a recently discovered gaseous transmitter, whose role in PSCs has not been explored yet. In the present study, we examined the effects of sodium hydrosulfide (NaHS), an H2S donor, on rat PSCs and elucidated the mechanisms involved.
Primary PSCs were isolated from rat pancreatic tissue. Lactate dehydrogenase and caspase assays were performed to detect cell death. Pancreatic stellate cell proliferation was determined by cell count analyses, bromodeoxyuridine incorporation, and flow cytometry. The role of heme oxygenase-1 (HO-1) was assessed by pharmacological HO inhibition and transfection of HO-1 small interfering RNA. Pancreatic stellate cell migration was determined by a wound healing assay, and PSC contraction was assessed by a gel contraction assay. α-Smooth muscle actin, collagen type I, and fibronectin messenger RNAs were analyzed by real-time polymerase chain reaction.
NaHS inhibited PSC proliferation at nontoxic concentrations. This was associated with HO-1-mediated repression of extracellular signal-regulated kinase 1/2 signaling. NaHS suppressed PSC migration and activation as well as extracellular matrix synthesis.
The results of the present study indicate that NaHS inhibits key cell functions of PSCs. Administration of H(2)S-releasing compounds might represent a novel strategy in the treatment of pancreatic fibrosis.
胰腺星状细胞（PSCs）在胰腺纤维化发展过程中起着至关重要的作用。硫化氢（H2S）是一种新发现的气体递质，其在 PSCs 中的作用尚未被探索。本研究旨在研究氢硫化钠（NaHS），一种 H2S 供体，对大鼠 PSCs 的影响，并阐明其涉及的机制。
从大鼠胰腺组织中分离原代 PSCs。通过乳酸脱氢酶和半胱天冬酶测定来检测细胞死亡。通过细胞计数分析、溴脱氧尿苷掺入和流式细胞术来确定胰腺星状细胞的增殖。通过药理学 HO 抑制和 HO-1 小干扰 RNA 转染来评估血红素加氧酶-1（HO-1）的作用。通过划痕愈合试验来确定胰腺星状细胞的迁移，通过凝胶收缩试验来评估 PSC 的收缩。通过实时聚合酶链反应分析α-平滑肌肌动蛋白、I 型胶原和纤维连接蛋白信使 RNA。
在非毒性浓度下，NaHS 抑制 PSC 增殖。这与 HO-1 介导的细胞外信号调节激酶 1/2 信号通路的抑制有关。NaHS 抑制 PSC 的迁移和激活以及细胞外基质的合成。
本研究结果表明，NaHS 抑制 PSCs 的关键细胞功能。H2S 释放化合物的给药可能代表治疗胰腺纤维化的一种新策略。
