Jensen Amanda R, Drucker Natalie A, Khaneki Sina, Ferkowicz Michael J, Markel Troy A
Section of Pediatric Surgery, Department of Surgery, Riley Hospital for Children at Indiana University Health, Indianapolis, Indiana.
Indiana University School of Medicine, Indianapolis, Indiana.
Am J Physiol Gastrointest Liver Physiol. 2017 May 1;312(5):G450-G456. doi: 10.1152/ajpgi.00444.2016. Epub 2017 Mar 9.
Hydrogen sulfide (HS) is an endogenous gasotransmitter that has vasodilatory properties. It may be a novel therapy for intestinal ischemia-reperfusion (I/R) injury. We hypothesized that ) HS would improve postischemic survival, mesenteric perfusion, mucosal injury, and inflammation compared with vehicle and ) the benefits of HS 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 µmol/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. values < 0.05 were significant. HS 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 HS therapy. Application of HS also resulted in lower levels of intestinal cytokine production following I/R. Intraperitoneal HS therapy can improve mesenteric perfusion, intestinal mucosal injury, and intestinal inflammation following I/R. The benefits of HS appear to be mediated through endothelial nitric oxide-dependent pathways. HS 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 HS works through nitric oxide-dependent pathways in the intestine. We appreciate that HS was able to improve postischemic recovery of mesenteric perfusion, mucosal integrity, and inflammation. The beneficial effects of HS appear to be mediated through endothelial nitric oxide-dependent pathways.
硫化氢（HS）是一种具有血管舒张特性的内源性气体递质。它可能是治疗肠道缺血再灌注（I/R）损伤的一种新疗法。我们假设：1）与赋形剂相比，HS能改善缺血后的存活率、肠系膜灌注、黏膜损伤和炎症；2）HS的益处将通过内皮型一氧化氮介导。将C57BL/6J野生型和内皮型一氧化氮合酶基因敲除（eNOS KO）小鼠麻醉后，行中线剖腹术。取出肠管，确定小肠肠系膜根部，并使用激光多普勒测定基线肠灌注。通过暂时阻断肠系膜上动脉建立肠缺血。缺血后，移除血管夹，让肠管恢复。将 PBS 赋形剂中的硫氢化钠（2 nmol/kg 或 2 µmol/kg NaHS）或仅赋形剂注入腹腔。让动物恢复，并评估肠系膜灌注、黏膜损伤和肠细胞因子。P<0.05为有显著性差异。HS改善了I/R损伤后的肠系膜灌注和黏膜损伤评分。然而，在eNOS缺失的情况下，HS治疗并未改善这些参数。应用HS还导致I/R后肠细胞因子产生水平降低。腹腔内给予HS治疗可改善I/R后的肠系膜灌注、肠黏膜损伤和肠道炎症。HS的益处似乎是通过内皮型一氧化氮依赖性途径介导的。HS是一种气体介质，作为一种抗炎剂有助于胃肠道黏膜防御。它促进血管舒张、黏膜修复以及肠缺血后炎症的消退，可能被开发为一种新型治疗药物。目前尚不清楚HS在肠道中是否通过一氧化氮依赖性途径发挥作用。我们认识到HS能够改善缺血后肠系膜灌注、黏膜完整性和炎症的恢复。HS的有益作用似乎是通过内皮型一氧化氮依赖性途径介导的。
