Carbon monoxide-releasing molecule-2 protects intestinal mucosal barrier function by reducing epithelial tight-junction damage in rats undergoing cardiopulmonary resuscitation  

作　　者：Qingsheng Niu Fang Liu Jun Zhang Xiaojun Yang Xiaohong Wang 

机构地区：[1]Department of Critical Care Medicine,General Hospital of Ningxia Medical University,Yinchuan,Ningxia Hui Autonomous Region 750004,China [2]Ningxia Medical University,Yinchuan,Ningxia Hui Autonomous Region 750004,China [3]Department of Critical Care Medicine,Heze Second People’s Hospital,Heze,Shandong 274000,China

出　　处：《Journal of Intensive Medicine》2022年第2期118-126,共9页重症医学（英文）

基　　金：supported by the National Natural Science Foundation of China(Grant No:81460288,81960348).

摘　　要：Background:Ischemia-reperfusion injury(IRI)to the small intestine is associated with the development of systemic inflammation and multiple organ failure after cardiopulmonary resuscitation(CPR).It has been reported that exogenous carbon monoxide(CO)reduces IRI.This study aimed to assess the effects of carbon monoxide-releasing molecule-2(CORM-2)on intestinal mucosal barrier function in rats undergoing CPR.Methods:We established a rat model of asphyxiation-induced cardiac arrest(CA)and resuscitation to study intestinal IRI,and measured the serum levels of intestinal fatty acid-binding protein.Morphological changes were investigated using light and electron microscopes.The expression levels of claudin 3(CLDN3),occludin(OCLN),zonula occludens 1(ZO-1),tumor necrosis factor-alpha(TNF-α),interleukin-10(IL-10),and nuclear factor kappa B(NF-κB)p65 were detected by western blotting.Results:Compared with the sham-operated group,histological changes and transmission electron microscopy revealed severe intestinal mucosal injury in the CPR and inactive CORM-2(iCORM-2)groups.In contrast,CORM-2 alleviated intestinal IRI.CORM-2,unlike iCORM-2,markedly decreased the Chiu’s scores(2.38±0.38 vs.4.59±0.34;P<0.05)and serum intestinal fatty acid-binding protein level(306.10±19.22 vs.585.64±119.84 pg/mL;P<0.05)compared with the CPR group.In addition,CORM-2 upregulated the expres-sion levels of tight junction proteins(CLDN3,OCLN,and ZO-1)(P<0.05)and downregulated those of IL-10,TNF-α,and NF-кB p65(P<0.05)in the ileum tissue of rats that received CPR.Conclusions:CORM-2 prevented intestinal mucosal damage as a result of IRI during CPR.The underlying protective mechanism was associated with inhibition of ischemia-reperfusion-induced changes in intestinal epithelial permeability and inflammation in intestinal tissue.

关 键 词：Carbon monoxide-releasing molecule-2 Cardiopulmonary resuscitation Intestinal mucosal barrier Tight junction Inflammation 

分 类 号：R654.1[医药卫生—外科学] R45[医药卫生—临床医学]