Delineating the relationships among the formation of reactive oxygen species, cell membrane instability and innate autoimmunity in intestinal reperfusion injury.
Delineating the relationships among the formation of reactive oxygen species, cell membrane instability and innate autoimmunity in intestinal reperfusion injury.
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DOI：
10.1016/j.molimm.2013.11.012
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发表时间：
2014-04
影响因子：
3.6
通讯作者：
Zhang M
中科院分区：
文献类型：
--
作者：
Lee H;Ko EH;Lai M;Wei N;Balroop J;Kashem Z;Zhang M
急性肠缺血是一种具有高死亡率的医学急症，证明需要更好地了解其发病机制并开发有效的治疗方法。本研究的目的是阐明肠缺血/再灌注（I/R）损伤的细胞内和细胞外事件之间的关系，特别是活性氧（ROS）的形成，与脂质过氧化相关的细胞膜不稳定性以及天然IgM和补体介导的先天性自身免疫反应。使用天然IgM介导的肠I/R的鼠模型。发现与WT对照相比，过表达抗氧化酶SOD 1的小鼠具有显著降低的肠组织损伤和IgM介导的补体激活的完全阻断。为了确定细胞膜不稳定性是否是ROS形成和天然IgM介导的先天性自身免疫应答之间的中间事件，在诱导肠缺血之前向WT小鼠施用细胞膜稳定剂（海藻糖）。海藻糖治疗显著保护动物免受I/R损伤，并抑制IgM介导的补体激活，但不能防止膜脂质过氧化。这些数据表明，在正常小鼠I/R损伤，细胞内ROS的形成是一个事件的脂质过氧化反应，导致细胞膜不稳定的上游。膜的不稳定性导致天然IgM和补体的先天性自身免疫反应。海藻糖是一种无毒的二糖，动物和人类耐受性良好，有望成为急性肠缺血相关疾病患者的保护剂。
Acute intestinal ischemia is a medical emergency with a high mortality rate, attesting to the need for a better understanding of its pathogenesis and the development of effective therapies. The goal of this study was to delineate the relationships among intracellular and extracellular events in intestinal ischemia/reperfusion (I/R) injury, particularly the formation of reactive oxygen species (ROS), cell membrane instability associated with lipid peroxidation and the innate autoimmune response mediated by natural IgM and complement. A murine model of natural IgM-mediated intestinal I/R was used. Mice overexpressing anti-oxidant enzyme SOD1 were found to have significantly reduced intestinal tissue damage and complete blockage of IgM-mediated complement activation compared with WT controls. To determine if cell membrane instability was an event intermediate between ROS formation and natural IgM-mediated innate autoimmune response, the cell membrane stabilizer (trehalose) was administered to WT mice prior to the induction of intestinal ischemia. Treatment with trehalose significantly protected animals from I/R injury and inhibited IgM-mediated complement activation although it did not prevent membrane lipid peroxidation. These data indicate that in normal mice subjected to I/R injury, intracellular ROS formation is an event upstream of the lipid peroxidation which results in cell membrane instability. The membrane instability leads to an innate autoimmune response by natural IgM and complement. Trehalose, a nontoxic disaccharide tolerated well by animals and humans, has promise as a protective agent for patients with medical conditions related to acute intestinal ischemia.
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影响因子：
7.1
作者：
Halliwell, Barry;Chirico, Susanna
通讯作者：
Chirico, Susanna
影响因子：
2.7
作者：
Cui, X. D.;Gao, D. Y.;Pu, L. L. Q.
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影响因子：
--
作者：
GRISHAM, MB;HERNANDEZ, LA;GRANGER, DN
通讯作者：
GRANGER, DN
影响因子：
6.2
作者：
Fukuse, T;Hirata, T;Wada, H
通讯作者：
Wada, H
影响因子：
4.4
作者：
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通讯作者：
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