Hydrogen sulfide improves intestinal recovery following ischemia by endothelial nitric oxide-dependent mechanisms
Hydrogen sulfide improves intestinal recovery following ischemia by endothelial nitric oxide-dependent mechanisms
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DOI：
10.1152/ajpgi.00444.2016
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发表时间：
2017-05-01
影响因子：
4.5
通讯作者：
Markel, Troy A.
中科院分区：
文献类型：
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作者：
Jensen, Amanda R.;Drucker, Natalie A.;Markel, Troy A.
硫化氢（H2S）是一种内源性气体递质，具有血管舒张特性。这可能是治疗肠缺血再灌注损伤的一种新方法。我们假设：1）与溶剂相比，H2S可改善缺血后存活率、肠系膜灌注、粘膜损伤和炎症; 2）H2S的益处将通过内皮一氧化氮介导。将C57 BL/6 J野生型和内皮型一氧化氮合酶敲除（eNOS KO）小鼠麻醉，并进行中线剖腹术。取出肠，确定小肠肠系膜根，并使用激光多普勒确定基线肠灌注。通过暂时闭塞上级肠系膜动脉建立肠缺血。在局部缺血后，移除夹子，并使肠恢复。将PBS载体中的硫氢化钠（2 nmol/kg或2 μ mol/kg NaHS）或仅载体注射到腹膜中。允许动物恢复，并评估肠系膜灌注、粘膜损伤和肠道细胞因子。P值< 0.05具有显著性。H2S改善I/R损伤后肠系膜灌注和粘膜损伤评分。然而，在eNOS消融的情况下，H2S治疗对这些参数没有改善。H2S的应用也导致I/R后肠道细胞因子产生水平降低。腹腔内硫化氢治疗可改善肠缺血再灌注后肠系膜血流灌注、肠粘膜损伤和肠道炎症。H2S的益处似乎是通过内皮一氧化氮依赖性途径介导的。新&值得注意的是H2S是一种气体介质，作为抗炎剂有助于胃肠道粘膜防御。它促进血管扩张、粘膜修复和肠道缺血后炎症的消退，并可能被开发为一种新的治疗剂。目前还不清楚H2S是否通过肠道中的一氧化氮依赖性途径起作用。我们认识到H2S能够改善肠系膜灌注、粘膜完整性和炎症的缺血后恢复。硫化氢的有益作用似乎是通过内皮一氧化氮依赖性途径介导的。
Hydrogen sulfide (H2S) is an endogenous gasotransmitter that has vasodilatory properties. It may be a novel therapy for intestinal ischemia-reperfusion (I/R) injury. We hypothesized that 1) H2S would improve postischemic survival, mesenteric perfusion, mucosal injury, and inflammation compared with vehicle and 2) the benefits of H2S would be mediated through endothelial nitric oxide. C57BL/6J wild-type and endothelial nitric oxide synthase knockout (eNOS KO) mice were anesthetized, and a midline laparotomy was performed. Intestines were eviscerated, the small bowel mesenteric root identified, and baseline intestinal perfusion was determined using laser Doppler. Intestinal ischemia was established by temporarily occluding the superior mesenteric artery. Following ischemia, the clamp was removed, and the intestines were allowed to recover. Either sodium hydrosulfide (2 nmol/kg or 2 mu mol/kg NaHS) in PBS vehicle or vehicle only was injected into the peritoneum. Animals were allowed to recover and were assessed for mesenteric perfusion, mucosal injury, and intestinal cytokines. P values < 0.05 were significant. H2S improved mesenteric perfusion and mucosal injury scores following I/R injury. However, in the setting of eNOS ablation, there was no improvement in these parameters with H2S therapy. Application of H2S also resulted in lower levels of intestinal cytokine production following I/R. Intraperitoneal H2S therapy can improve mesenteric perfusion, intestinal mucosal injury, and intestinal inflammation following I/R. The benefits of H2S appear to be mediated through endothelial nitric oxide-dependent pathways.NEW & NOTEWORTHY H2S is a gaseous mediator that acts as an anti-inflammatory agent contributing to gastrointestinal mucosal defense. It promotes vascular dilation, mucosal repair, and resolution of inflammation following intestinal ischemia and may be exploited as a novel therapeutic agent. It is unclear whether H2S works through nitric oxide-dependent pathways in the intestine. We appreciate that H2S was able to improve postischemic recovery of mesenteric perfusion, mucosal integrity, and inflammation. The beneficial effects of H2S appear to be mediated through endothelial nitric oxide-dependent pathways.