Hydrogen Sulfide Protects Against Ischemia-Reperfusion Injury in an In Vitro Model of Cutaneous Tissue Transplantation

Hydrogen Sulfide Protects Against Ischemia-Reperfusion Injury in an In Vitro Model of Cutaneous Tissue Transplantation
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DOI:
10.1016/j.jss.2009.05.010
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发表时间:
2010-03-01
影响因子:
2.2
通讯作者:
Spector, Jason A.
Spector, Jason A.
中科院分区:
医学3区
文献类型:
--
作者:
Henderson, Peter W.;Singh, Sunil P.;Spector, Jason A.

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背景缺血-再灌注损伤(IRI)是许多临床情况下发病率和死亡率的来源,并且作为其许多后果之一,诱导细胞凋亡。硫化氢(H2S)可以以可逆、无毒的方式降低细胞代谢。建立了一种体外皮肤组织移植模型,以评估H2S是否可以减轻IR引起的细胞损伤。人脐静脉内皮细胞(HUVEC)用含有NaHS(0、10 μ M、100 μ M或1 mM)的培养基处理,并暴露于常氧(21%氧)、缺氧(1%)或缺氧(0%)。然后将细胞恢复至常氧状态,并使用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记(TUNEL)测定法定量细胞凋亡。成纤维细胞(3 T3)用硫化氢处理,并以类似的方式暴露于缺氧。H2S处理导致IRI后HUVECs和3 T3细胞凋亡显著减少。未观察到H2S的毒性,但在较高剂量下保护作用不太明显。这是第一个研究H2S和皮瓣的细胞成分在IRI的设置。我们的研究结果表明,H2S显着减少细胞凋亡在体外的设置IRI。这些数据表明,H2S可以减轻体内IRI,因此有潜力作为改善临床情况下组织生存能力的疗法。(C)2010年爱思唯尔公司All rights reserved.
Background. Ischemia-reperfusion injury (IRI) is a source of morbidity and mortality in many clinical scenarios, and has as one of its many consequences the induction of cellular apoptosis. Hydrogen sulfide (H2S) may decrease cellular metabolism in a reversible, nontoxic manner. An in vitro model of cutaneous tissue transplantation was developed to assess whether H2S could ameliorate cellular injury caused by IRI.Methods. Human umbilical vein endothelial cells (HUVECs) were treated with media containing NaHS (0, 10 mu M, 100 mu M, or 1 mM) and exposed to normoxia (21% oxygen), hypoxia (1%), or anoxia (0%). Cells were then returned to normoxia, and apoptosis was quantified using a terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Fibroblasts (3T3s) were treated with H2S and exposed to anoxia in a similar fashion.Results. Treatment with H2S resulted in a significant decrease in apoptosis in HUVECs and 3T3s subjected to IRI. Toxicity of H2S was not observed, although the protective effect was less evident at higher doses.Conclusion. This is the first study to examine H2S and the cellular components of cutaneous flaps in the setting of IRI. Our results demonstrate that H2S significantly decreases apoptosis in vitro in the setting of IRI. These data suggest H2S may mitigate IRI in vivo, and, therefore, has potential as a therapy for improving tissue survivability in clinical scenarios. (C) 2010 Elsevier Inc. All rights reserved.