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.
Inflamm Res. 2015 Jun;64(6):395-403. doi: 10.1007/s00011-015-0817-x. Epub 2015 May 1.
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.
Mice underwent a 2 cm midline laparotomy, and the superior mesenteric artery (SMA) was obstructed by micro-vascular clamp to induce intestinal ischemia.
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.
Our study provides evidence HG regulates Nrf2-HO-1-Hmgb1 axis and attenuates intestinal IR injury in mice.
肠缺血再灌注（IR）综合征是由多种事件引起的危及生命的难题。盐酸育亨宾（HG）是乌头碱的一种活性成分，在东方国家传统上被用作心脏兴奋剂和抗炎药。但 HG 对肠道 IR 损伤的作用从未被研究过。
小鼠行 2cm 中线剖腹术，用微血管夹阻塞肠系膜上动脉（SMA）以诱导肠缺血。
在我们目前的研究中，HG 通过体外诱导血红素加氧酶-1（HO-1）的产生，增加了小鼠肠上皮（IEC-6）细胞的活力。在我们的体内小鼠肠道 IR 损伤模型中，HG 增加的 HO-1 蛋白水平和活性、降低的肠道损伤评分、髓过氧化物酶（MPO）活性和炎症细胞因子表达，均被 HO-1 抑制剂锌原卟啉 IX（ZnPPIX）的额外治疗所消除。此外，HG 降低了在 IR 损伤的肠组织中高迁移率族蛋白 B1（Hmgb1）的表达，而 ZnPPIX 的额外给药则抑制了其表达。并且，HG 处理明显降低了核因子红细胞 2 相关因子（Nrf-2）siRNA 转染细胞中的 HO-1 表达，但对对照 siRNA 转染细胞没有影响。
我们的研究提供了证据表明 HG 调节 Nrf2-HO-1-Hmgb1 轴，并减轻了小鼠的肠道 IR 损伤。
