Chao Liu1, Chenyu Zhu, Guangsheng Wang, Rui Xu, Yaoming Zhu. 1. Department of General Surgery, Yichang Central People's Hospital, The First College of Clinical Medical Science, China Three Gorges University, No.183, Yiling Road, Yichang, 443003, Hubei, China.
Abstract
INTRODUCTION: 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-inflammatory 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 inflammatory 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 significantly 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.
INTRODUCTION: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-inflammatory 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 inflammatory 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 significantly 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.
Authors: Yu Mi Ha; Min Young Kim; Min Kyu Park; Young Soo Lee; Young Min Kim; Hye Jung Kim; Jae Heun Lee; Ki Churl Chang Journal: Apoptosis Date: 2012-05 Impact factor: 4.677
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