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中华普通外科学文献(电子版) ›› 2013, Vol. 07 ›› Issue (04) : 278 -283. doi: 10.3877/cma.j.issn.1674-0793.2013.04.009

所属专题: 文献

论著

全反式维甲酸在小肠缺血再灌注中的炎症抑制效应及机制
陈图锋1, 华赟鹏2, 黄婵燕3, 王钟兴3,()   
  1. 1. 510630 广州,中山大学附属第三医院胃肠外科
    2. 中山大学附属第一医院肝胆外科
    3. 中山大学附属第一医院麻醉科
  • 收稿日期:2013-01-09 出版日期:2013-08-01
  • 通信作者: 王钟兴
  • 基金资助:
    广东省科技计划资助项目(2010B031600206); 广东省自然科学基金资助项目(10151008901000113)

All trans Retinoic Acid contributes to the reduction of inflammation in intestinal ischemia/reperfusion injury

Tu-feng CHEN1, Yun-peng HUA2, Chan-yan HUANG3, Zhong-xing WANG3,()   

  1. 1. Department of Gastrointestinal Surgery, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
  • Received:2013-01-09 Published:2013-08-01
  • Corresponding author: Zhong-xing WANG
  • About author:
    Corresponding author: WANG Zhong-xing, Email:
引用本文:

陈图锋, 华赟鹏, 黄婵燕, 王钟兴. 全反式维甲酸在小肠缺血再灌注中的炎症抑制效应及机制[J/OL]. 中华普通外科学文献(电子版), 2013, 07(04): 278-283.

Tu-feng CHEN, Yun-peng HUA, Chan-yan HUANG, Zhong-xing WANG. All trans Retinoic Acid contributes to the reduction of inflammation in intestinal ischemia/reperfusion injury[J/OL]. Chinese Archives of General Surgery(Electronic Edition), 2013, 07(04): 278-283.

目的

探讨全反式维甲酸(ATRA)对大鼠小肠缺血再灌注的炎症抑制作用和机制。

方法

24只雄性SD大鼠,每组8只,随机分为假手术组、阻断组和ATRA组。ATRA组术前以ATRA 15 mg?kg-1?d-1灌胃,阻断组以等体积溶媒二甲基亚砜(DMSO)灌胃,共5 d。术中阻断肠系膜上动脉60 min后再灌注120 min,收集各组大鼠末端回肠和血清。光学显微镜下观察回肠病理学改变、行肠黏膜Chiu氏评分;比色法测定血清二胺氧化酶(DAO)含量和回肠组织髓过氧化物酶(MPO)活性;ELISA法测定回肠组织肿瘤坏死因子α(TNF-α)及白介素1β(IL-1β)水平;Western blot检测回肠组织中胞核NF-κB p65蛋白和胞质NF-κB抑制蛋白α(IκBα)的表达量。

结果

与阻断组相比,ATRA组回肠黏膜病理损伤减轻,Chiu氏评分下降[(2.54±0.69) vs. (3.86±0.83),P < 0.05],血清DAO含量减少[(18.09±4.21)U/L vs. (24.56±4.92)U/L,P < 0.05],组织TNF-α[(61.37±18.66)pg/g vs. (97.21±24.67) pg/g]、IL-1β水平[(115.24±30.82)pg/g vs. (219.83±54.31)pg/g]和MPO活性[(4.62±1.18) U/g vs. (7.16±1.50) U/g]降低,均P < 0.05;胞核NF-κB p65蛋白表达下调[(3.71±0.83) vs. (6.59±1.05),P < 0.05],胞质IκBα蛋白含量增加[(0.56±0.12) vs. (0.26±0.05),P < 0.05]。

结论

ATRA预处理可以抑制NF-κB的激活,减轻组织的过度炎症反应,对大鼠小肠缺血再灌注损伤具有保护作用。

Objective

To investigate the anti-inflammatory effect and mechanism of all trans retinoic acid (ATRA) on intestinal ischemia/reperfusion (I/R) injury induced by superior mesenteric artery occlusion (SMAO).

Methods

Twenty-four Sprague-Dawley male rats were randomly divided into three groups (8 in each group): Sham group, I/R group and ATRA pretreatment group. Rat intestinal I/R models were made by clamping superior mesenteric artery for 60 min. After allowing reperfusion for 120 min, samples of distal ileum and serum were collected. Histological changes and Chiu's scores on the ileum mucosa were evaluated under light microscope. Serum diamine oxidase (DAO) and ileum myeloperoxidase (MPO) activity were analyzed by colorimetry. Ileum tumor necrosis factor (TNF)-α and interleukin(IL)-1β were detected by enzyme-linked immunosorbent assay method. Ileum protein of nuclear factor kappa B (NF-κB) p65 in nucleus and inhibitor NF-κB-α (IκBα) in cytoplasm was assessed by Western blot.

Results

Compared with I/R group, ATRA significantly downgraded the mucosal Chiu's scores [(2.54±0.69) vs. (3.86±0.83), P < 0.05], lessened the serum DAO content [(18.09±4.21)U/L vs. (24.56±4.92)U/L, P < 0.05], suppressed the NF-κB p65 expression [(3.71±0.83) vs. (6.59±1.05), P < 0.05] and increased the IκBα expression [(0.56±0.12) vs. (0.26±0.05), P < 0.05] in ileum. Subsequently, the levels of TNF-α and IL-1β or the activity of MPO in ileum were effectively reduced [(61.37±18.66)pg/g vs. (97.21±24.67) pg/g, P<0.05; (115.24±30.82)pg/g vs. (219.83±54.31) pg/g, P < 0.05; (4.62±1.18) U/g vs. (7.16±1.50) U/g, P < 0.05; respectively].

Conclusion

With the mechanism of inhibiting NF-κB activation, ATRA pretreatment can alleviate the excessive inflammation response which result in attenuating intestinal ischemia/reperfusion injury induced by SMAO in rat.

图1 各组回肠病理学改变(HE染色,×100)
图2 各组回肠黏膜Chiu氏评分(A)及血清DAO含量(B)的变化
图3 各组回肠组织TNF-α和IL-1β水平的变化
图4 各组回肠组织MPO活性的变化
图5 各组回肠组织胞核NF-κB p65蛋白(A)、胞质IκBα蛋白(B)的表达条带及表达量的变化
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