一氧化碳释放分子2对休克大鼠肠黏膜上皮屏障的保护作用

被引:7
作者
王晓红 [1 ]
刘芳 [2 ]
张胜 [2 ]
马希刚 [1 ]
机构
[1] 宁夏医科大学总医院重症医学科,银川
[2] 宁夏医科大学,银川
关键词
一氧化碳释放分子2; 休克; 肠; 紧密连接; 炎症;
D O I
暂无
中图分类号
R459.7 [急症、急救处理];
学科分类号
100231 [临床病理学];
摘要
目的探讨一氧化碳释放分子-2(CORM-2)对休克肠屏障损伤的保护作用。方法采用Wiggers改良法制备失血性休克大鼠模型, 32只SD大鼠随机(随机数字法)分为4组:假手术组、休克组、CORM-2组及iCORM-2组(灭活型CORM-2组), 每组各8只。CORM-2组及iCORM-2组干预药物均为5 mg/kg制作休克模型前1 h腹腔注射;各组于术后或制作休克模型24 h后留取回肠组织观察病理形态及超微结构;Western-blot检测回肠组织ZO-1、Occludin、Claudin3蛋白表达;ELISA法测定血D-乳酸及TNF-α含量。各组间采用单因素方差分析, 组间两两比较采用LSD-t检验,方差不齐时采用Kruskal Wallis秩和检验, 以P<0.05为差异有统计学意义。结果 (1)休克组大鼠回肠黏膜病理形态和超微结构损伤明显。CORM-2可明显改善休克大鼠肠黏膜病理形态和超微结构完整性。(2)与假手术组比较, 休克组和iCORM-2组的Claudin3、Occludin、ZO-1蛋白表达均降低(均P<0.05), CORM-2组仅Claudin3、ZO-1蛋白表达降低(均P<0.05)。CORM-2组上述蛋白表达均高于休克组及iCORM-2组(均P<0.05)。(3)与假手术组比较, 休克组和iCORM-2组血D-乳酸及TNF-α水平明显升高[D-乳酸(ng/mL)分别为139.49±28.83, 135.75±25.19vs 65.09±33.16;TNF-α(pg/mL)分别为358.60(314.18, 395.73), 312.25(275.75, 345.40)vs 65.85(47.82, 84.32), 均P<0.05]。CORM-2组血D-乳酸及TNF-α水平有升高趋势, 但差异无统计学意义[D-乳酸(ng/mL)75.65±34.14vs 65.09±33.16;TNF-α(pg/mL)104.00(93.10, 131.95)vs 65.85(47.82, 84.32), 均P>0.05]。CORM-2组血D-乳酸及TNF-α水平均低于休克组和iCORM-2组(均P<0.05)。结论 CORM-2可减轻休克肠屏障损伤, 并上调肠上皮紧密连接蛋白表达, 其抗炎效应可能是其发挥保护作用的机制之一。
引用
收藏
相关论文
共 15 条
[1]
Carbon Monoxide-Releasing Molecule-2 Reduces Intestinal Epithelial Tight-Junction Damage and Mortality in Septic Rats..[J].Shulong Zhang;Shuyun Zheng;Xin Wang;Qiankun Shi;Xiang Wang;Shoutao Yuan;Guozheng Wang;Zhenling Ji.PLoS ONE.2017, 12
[2]
Therapeutic roles of carbon monoxide in intestinal ischemia‐reperfusion injury.[J].Kazuhiro Katada;Tomohisa Takagi;Kazuhiko Uchiyama;Yuji Naito.J Gastroenterol Hepatol.2015,
[3]
Intestinal permeability - a new target for disease prevention and therapy [J].
Bischoff, Stephan C. ;
Barbara, Giovanni ;
Buurman, Wim ;
Ockhuizen, Theo ;
Schulzke, Joerg-Dieter ;
Serino, Matteo ;
Tilg, Herbert ;
Watson, Alastair ;
Wells, Jerry M. .
BMC GASTROENTEROLOGY, 2014, 14
[4]
Can serum L-lactate, D-lactate, creatine kinase and I-FABP be used as diagnostic markers in critically ill patients suspected for bowel ischemia [J].
van der Voort, Peter H. J. ;
Westra, Berit ;
Wester, Jos P. J. ;
Bosman, Rob J. ;
van Stijn, Ilse ;
Haagen, Inez-Anne ;
Loupatty, Ference J. ;
Rijkenberg, Saskia .
BMC ANESTHESIOLOGY, 2014, 14
[5]
Beneficial effects of ulinastatin on gut barrier function in sepsis..[J].Jiang Longyuan;Yang Lianhong;Zhang Meng;Fang Xiangshao;Huang Zitong;Yang Zhengfei;Zhou Tianen.The Indian journal of medical research.2013, 6
[6]
The therapeutic potential of carbon monoxide [J].
Motterlini, Roberto ;
Otterbein, Leo E. .
NATURE REVIEWS DRUG DISCOVERY, 2010, 9 (09) :728-U24
[7]
Cytokine regulation of tight junctions.[J].Christopher T. Capaldo;Asma Nusrat.BBA - Biomembranes.2008, 4
[8]
Protection of transplant-induced hepatic ischemia/reperfusion injury with carbon monoxide via MEK/ERK1/2 pathway downregulation [J].
Kaizu, Takashi ;
Ikeda, Atsushi ;
Nakao, Atsunori ;
Tsung, Allan ;
Toyokawa, Hideyoshi ;
Ueki, Shinya ;
Geller, David A. ;
Murase, Noriko .
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 2008, 294 (01) :G236-G244
[9]
Reducing small intestinal permeability attenuates colitis in the IL10 gene-deficient mouse.[J].M CArrieta;KMadsen;JDoyle;JMeddings.Gut.2008, 1
[10]
Carbon monoxide-releasing molecules (CO-RMs): vasodilatory; anti-ischaemic and anti-inflammatory activities..[J].Motterlini R.Biochemical Society transactions.2007, Pt 5