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Inamm. Res. (2015) 64:395403DOI 10.1007/s00011-015-0817-x Inammation Research
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Web End = Higenamine regulates Nrf2-HO-1-Hmgb1 axis and attenuates intestinal ischemiareperfusion injury in mice
Chao Liu1 Chenyu Zhu1 Guangsheng Wang1 Rui Xu1 Yaoming Zhu1
Received: 3 August 2014 / Revised: 12 March 2015 / Accepted: 2 April 2015 / Published online: 1 May 2015 Springer Basel 2015
AbstractIntroduction Intestinal ischemia and reperfusion (IR) syndrome is a life-threatening dilemma caused by diverse events. Higenamine (HG), an active ingredient of Aconiti Lateralis Radix Praeparata, has been traditionally used as a heart stimulant and anti-inammatory agent in oriental countries. But the function of HG on intestine IR injury has never been investigated.
Materials and methods Mice underwent a 2 cm midline laparotomy, and the superior mesenteric artery (SMA) was obstructed by micro-vascular clamp to induce intestinal ischemia.
Results In our current study, HG increases mouse intestinal epithelial (IEC-6) cell viability through induced heme oxygenase-1 (HO-1) production in vitro. In our in vivo murine intestinal IR injury model, the increased HO-1 protein level and activity, decreased intestinal injury score, Myeloperoxidase (MPO) activity, and inammatory cytokine expression induced by HG were all abolished with additional treatment of HO-1 inhibitor zinc protoporphyrin IX (ZnPPIX). Furthermore, HG reduced high mobility group box-1 (Hmgb1) expression in IR injury-performed intestine which was inhibited by additional administration of ZnPPIX. And HG treatment signicantly decreased HO-1 expression in nuclear factor erythroid 2-related factor
(Nrf-2) SiRNA-transfected cells but not in control SiRNA-transfected cells.
Conclusion Our study provides evidence HG regulates Nrf2-HO-1-Hmgb1 axis and attenuates intestinal IR injury in mice.
Keywords Higenamine Nrf-2 HO-1 Hmgb1
Intestinal IR injury
Introduction
Intestinal ischemia and reperfusion (IR) syndrome is a life-threatening dilemma caused by diverse events, including intestinal intussusception and transplantation, neonatal necrotizing enterocolitis, acute mesenteric arterial occlusion, and hemodynamic shock [1]. Intestinal ischemia results in impaired blood ow and local and systemic inammation, but restorations of the blood ow intensify ischemia-caused damage and leads to multiple organ failure (MOF) [2]. Although the detailed mechanisms responsible for IR injury of the small intestine remain...