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5mg/kg制作休克模型前1h腹腔注射;各组于术后或制作休克模型24h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±25.19vs65.09±33.16;TNF-α(pg/mL)分别为358.60(314.18,395.73),312.25(275.75,345.40)vs65.85(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±34.14vs65.09±33.16;TNF-α(pg/mL)104.00(93.10,131.95)vs65.85(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。
Objective To investigate the protective effect of carbon monoxide release molecule-2 (CORM-2)on intestinal barrier injury in shock rats.Methods Thirty-two rats were equally and randomly divided into 4groups:the sham operated group,shock group,carbon monoxide releasing molecule-2(CORM-2) group and inactivated CORM-2(iCORM-2)group.A modified Wiggers model was used in inducing hemorrhagic shock.In the CORM-2 group and iCORM-2 group,the animals were intraperitoneally injected CORM-2(5mg/kg)or iCORM-2(5mg/kg)I h before inducing shock.The ileum tissues were harvested 24h after operation or 24h after inducing shock,and the histopathologic changes and ultrastructure of the ileum were observed.The expressions of ZO-1,Occludin,and Claudin3 protein in ileum intestinal mucosa were determined by Westem blot.TNF-α and D-lactic acid levels in the blood were measured by enzyme-linked immunosorbent assay (ELISA).Data of multi-groups were analyzed by one way variance (ANOVA)and inter-group comparisons were made by the least significant difference (LSD)-t tests.Kruskal Wallis rank sum test was used when homogeneity of variance were not met.The value of P<0.05 was considered statistically significant.Results (1)The pathological changes and ultrastructural damage of ileum mucosa in the shock group were obvious.CORM-2 can significantly improve the pathological morphology and ultrastructural integrity of intestinal mucosa in shock rats. (2)Compared with the sham operated group,the expressions of Claudin3,Occludin,and ZO-1 of ileum intestinal mucosa were significantly decreased in the shock group and iCORM-2group(all P<0.05), but in the CORM-2 group,only the expression of Claudin3 and ZO-1 were decreased(P<0.05).The expression of these proteins in the CORM-2 group was higher than that in the shock group and iCORM-2 group.(3)Compared with the sham operated group,the levels of D-lactic acid and TNF-α in the shock group and iCORM-2group were significantly higher[D-lactic acid(ng/mL):139.49±28.83,135.75±25.19vs 65.09±33.16;TNF-α (pg/m
作者
王晓红
刘芳
张胜
马希刚
Wang Xiaohong;Liu Fang;Zhang Sheng;Ma Xigang(Department of lntensive Care Unit,General Hospital of Ningxia Medical University,Yinchuan 750004,China;Ningxia Medical University,Yinchuan 750004,China)
出处
《中华急诊医学杂志》
CAS
CSCD
北大核心
2019年第1期50-55,共6页
Chinese Journal of Emergency Medicine
基金
宁夏自然科学基金(2018AAC03143)
国家自然科学基金(81460288).
关键词
一氧化碳释放分子2
休克
肠
紧密连接
炎症
Carbon monoxide releasing molecule-2
Shock
Intestinal
Tight junction
Inflammation
