Heme oxygenase-1 induction by hemin protects against gut ischemia/reperfusion injury

Heme oxygenase-1 induction by hemin protects against gut ischemia/reperfusion injury
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DOI:
10.1016/j.jss.2004.01.010
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发表时间:
2004-05-01
影响因子:
2.2
通讯作者:
Moore, FA
Moore, FA
中科院分区:
医学3区
文献类型:
--
作者:
Attuwaybi, BO;Kozar, RA;Moore, FA

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背景。我们已经证明,缺血内低温和高渗盐水复苏均可对部分由血红素加氧酶-1 (HO-1) 介导的肠道缺血/再灌注 (I/R) 损伤提供显着保护。因此,我们假设血红素诱导 HO-1 会减轻肠道 I/R 后的损伤并改善功能。材料和方法。雄性Sprague-Dawley大鼠在肠系膜上动脉闭塞60分钟或假剖腹手术前2小时用50μmol/kg氯高铁血红素(HO-1诱导剂原卟啉IX氯化物)sq或媒介物治疗2小时。再灌注 6 小时后,通过在注射到十二指肠后 30 分钟(表示为平均几何中心)对小肠 10 个相等段中的示踪剂百分比进行定量来确定转运。收获回肠用于评估粘膜组织学损伤(盲法观察者的 Chin 评分 0-5)、髓过氧化物酶活性(MPO,炎症指数)和 HO-1 蛋白表达。结果。氯化血红素治疗与 HO-1 蛋白表达增加、粘膜损伤减轻、MPO 活性降低以及肠道 I/R 后肠道转运改善相关。结论。这些数据证实 HO-1 在保护肠道免受缺血再灌注引起的损伤方面发挥着重要作用。 (C) 2004 Elsevier Inc. 保留所有权利。
Background. We have shown that both intraischemic hypothermia and hypertonic saline resuscitation provide dramatic protection against gut ischemia/reperfusion (I/R) injury that is in part mediated by heme oxygenase-1 (HO-1). We therefore hypothesized that induction of HO-1 by hemin would lessen damage and improve function after gut I/R.Materials and methods. Male Sprague-Dawley rats were treated with 50 mumol/kg hemin (HO-1 inducer ferric protoporphyrin IX chloride) sq or vehicle 2 h before superior mesenteric artery occlusion for 60 min or sham laparotomy. After 6 h of reperfusion, transit was determined by quantitation of percentage of tracer in 10 equal segments of small intestine 30 min following injection into the duodenum (expressed as mean geometric center). Ileum was harvested for assessment of mucosal histologic injury (Chin score 0-5 by blinded observer), myeloperoxidase activity (MPO, index of inflammation), and HO-1 protein expression.Results. Hemin treatment was associated with increased HO-1 protein expression, lessened mucosal injury, decreased MPO activity, and improved intestinal transit following gut I/R.Conclusion. These data corroborate that HO-1 plays an important role in protecting the gut against I/R-induced injury. (C) 2004 Elsevier Inc. All rights reserved.