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

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ATRA15mg·kg-1·d。灌胃，阻断组以等体积溶媒二甲基亚砜（DMSO）灌胃，共5d。术中阻断肠系膜上动脉60rain后再灌注120min，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仅（TNF-a）及白介素1B（IL-1β）水平；Westernblot检测回肠组织中胞核NF—KBp65蛋白和胞质NF—KB抑制蛋白d（IKBd）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）US．（3．86±0．83），P〈0．05]，血清DAO含量减少（18．09±4．21）U／LUS．（24．56±4．92）U／L，P〈0．05]，组织TNF-d（61．37±18．66）pg／g135．（97．21±24．67）Pg／g]、IL—1β水平（115．24±30．82）pg／gcs．（219．83±54．31）pg／g]和MPO活性（4．62±1．18）U／gUS．（7．16±1．50）U／g]降低，均P〈0．05；胞核NF—KBp65蛋白表达下调（3．71±0．83）vs．（6．59±1．05），P〈0．051，胞质IKB仪蛋白含量增加（0．56±0．12）vs．（0．26±0．05），P〈0．05]。结论ATRA预处理可以抑制NF—KB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。

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

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 rain. 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）- a and interleukin（IL）- 1 5 were detected by enzyme-linked immunosorbent assay method. Ileum protein of nuclear factor kappa B （NF- t〈 B） p65 in nucleus and inhibitor NF- K B- ct （I K B a ） 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- K B p65 expression （3.71 ±0.83） vs. （6.59 ± 1.05）, P 〈 0.05] and increased the I K B a expression （0.56 ± 0.12） vs. （0.26 ±0.05）, P 〈 0.05] in ileum. Subsequently, the levels of TNF- aand IL-113 or the activity of MPO in ileum were effectively reduced （61.37 ± 18.66）pg/g vs. （97.21 ± 24.67） pg/g,P〈O.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]. Coneluslon With the mechanism of inhibiting NF- K B activation, ATRA pretreatment can alleviate the excessive inflammation response which result in attenuating intestinal ischemia/reperfusion injury induced by SMAO in rat.