切换至 "中华医学电子期刊资源库"

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]. 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]. 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
1
Tsukamoto T, Chanthaphavong RS, Pape HC. Current theories on the pathophysiology of multiple organ failure after trauma. Injury, 2010, 41(1): 21-26.
2
Fournier BM, Parkos CA. The role of neutrophils during intestinal inflammation. Mucosal Immunol, 2012, 5(4): 354-366.
3
Ozdemir R, Yurttutan S, Sari FN, et al. All-Trans-Retinoic Acid Attenuates Intestinal Injury in a Neonatal Rat Model of Necrotizing Enterocolitis. Neonatology, 2013, 104(1): 22-27.
4
Nozaki Y, Yamagata T, Sugiyama M, et al. Anti-inflammatory effect of all-trans retinoic acid in inflammatory arthritis. Clin Immunol, 2006, 119(3): 272-279.
5
Chiu CJ, McArdle AH, Brown R, et al. Intestinal mucosal lesion in low-flow states. I. A morphological, hemodynamic, and metabolic reappraisal. Arch Surg, 1970, 101(4): 478-483.
6
陈元岩,李天翔,陈显国, 等. 血必净联合维拉帕米对大鼠小肠缺血再灌注损伤的实验研究[J/CD]. 中华普通外科学文献:电子版,2013, 7(1): 7-11.
7
Moriyama K, Kouchi Y, Morinaga H, et al. Diamine oxidase, a plasma biomarker in rats to GI tract toxicity of oral fluorouracil anti-cancer drugs. Toxicology, 2006, 217(2-3): 233-239.
8
Gille J, Paxton LL, Lawley TJ, et al. Retinoic acid inhibits the regulated expression of vascular cell adhesion molecule-1 by cultured dermal microvascular endothelial cells. J Clin Invest, 1997, 99(3): 492-500.
9
Wojtal KA, Wolfram L, Frey-Wagner I, et al. The effects of vitamin A on cells of innate immunity in vitro. Toxicol In Vitro, 2013, 27(5): 1525-1532.
10
Lawrence T. The nuclear factor NF-kappaB pathway in inflammation. Cold Spring Harb Perspect Biol, 2009, 1(6): a001651.
11
Wan X, Li X, Bo H, et al. All-trans retinoic acid protects renal tubular epithelial cells against hypoxia induced injury in vitro. Transplant Proc, 2013, 45(2): 497-502.
12
Nizamutdinova IT, Guleria RS, Singh AB, et al. Retinoic acid protects cardiomyocytes from high glucose-induced apoptosis through inhibition of NF-κB signaling pathway. J Cell Physiol, 2013, 228(2): 380-392.
13
Molestina RE, Payne TM, Coppens I, et al. Activation of NF-kappaB by Toxoplasma gondii correlates with increased expression of antiapoptotic genes and localization of phosphorylated IkappaB to the parasitophorous vacuole membrane. J Cell Sci, 2003, 116(Pt 21): 4359-4371.
[1] 韩圣瑾, 周正武, 翁云龙, 黄鑫. 碳酸氢钠林格液联合连续性肾脏替代疗法对创伤合并急性肾损伤患者炎症水平及肾功能的影响[J]. 中华危重症医学杂志(电子版), 2023, 16(05): 376-381.
[2] 陈大敏, 曹晓刚, 曹能琦. 肥胖对胃癌患者手术治疗效果的影响研究[J]. 中华普外科手术学杂志(电子版), 2023, 17(06): 651-653.
[3] 贾成朋, 王代宏, 陈华, 孙备. 可切除性胰腺癌预后术前预测模型的建立及应用[J]. 中华普外科手术学杂志(电子版), 2023, 17(05): 566-570.
[4] 王博, 郭利君, 李二强, 张贺林, 徐鹏, 杨晓春. 消化道与口腔黏膜组织在输尿管重建中的研究进展[J]. 中华腔镜泌尿外科杂志(电子版), 2023, 17(05): 434-439.
[5] 伍学成, 李远伟, 袁武雄, 王建松, 石泳中, 卢强, 李卓, 陈佳, 刘哲, 滕伊漓, 高智勇. 炎症介质谱联合降钙素原在尿源性脓毒血症中的诊断价值[J]. 中华腔镜泌尿外科杂志(电子版), 2023, 17(05): 476-480.
[6] 王可, 范彬, 李多富, 刘奎. 两种疝囊残端处理方法在经腹腹膜前腹股沟疝修补术中的疗效比较[J]. 中华疝和腹壁外科杂志(电子版), 2023, 17(06): 692-696.
[7] 关明函, 薛志强. 右美托咪定改善大鼠脑缺血再灌注后脑损伤的研究[J]. 中华神经创伤外科电子杂志, 2023, 09(05): 270-276.
[8] 邹勇, 顾应江, 丁昊, 杨呈浩, 陈岷辉, 蔡昱. 基于Nrf2/HO-1及NF-κB信号通路探讨葛根素对大鼠脑出血后早期炎症反应及氧化应激反应的影响[J]. 中华脑科疾病与康复杂志(电子版), 2023, 13(05): 271-277.
[9] 屈霄, 王靓, 陆萍, 何斌, 孙敏. 外周血炎症因子及肠道菌群特征与活动性溃疡性结肠炎患者病情的相关性分析[J]. 中华消化病与影像杂志(电子版), 2023, 13(06): 466-470.
[10] 杨忠华, 马晓菡, 刁磊, 胡静, 陈熙. 双气囊小肠镜在小肠CT造影结果阴性患者中的诊断价值[J]. 中华消化病与影像杂志(电子版), 2023, 13(06): 475-479.
[11] 朱风尚, 舍玲, 丁永年, 杨长青. 警惕炎症性肠病与少见肠道疾病的鉴别诊断[J]. 中华消化病与影像杂志(电子版), 2023, 13(05): 273-276.
[12] 邱春华, 张志宏. 1108例小肠疾病的临床诊断及检查策略分析[J]. 中华临床医师杂志(电子版), 2023, 17(9): 948-954.
[13] 张敏洁, 张小杉, 段莎莎, 施依璐, 赵捷, 白天昊, 王雅晳. 氢气治疗心肌缺血再灌注损伤的作用机制及展望[J]. 中华临床医师杂志(电子版), 2023, 17(06): 744-748.
[14] 张赟辉, 罗军, 刘栗丽, 汪宏, 耿克明. 腹膜透析与血液透析对老年终末期肾病患者营养状况及炎症反应的影响[J]. 中华临床医师杂志(电子版), 2023, 17(04): 419-423.
[15] 刘感哲, 艾芬. MiRNA-210通过抑制HIF-1α的表达改善大鼠血管性认知功能障碍[J]. 中华脑血管病杂志(电子版), 2023, 17(05): 489-494.
阅读次数
全文


摘要