5-氨基水杨酸治疗结肠炎的抗氧化作用及对细胞因子表达的影响

中国临床药理学与治疗学 ›› 2005, Vol. 10 ›› Issue (12): 1344-1348.

5-氨基水杨酸治疗结肠炎的抗氧化作用及对细胞因子表达的影响

张林, 夏冰, 程虹

武汉大学中南医院内科, 武汉大学医学院消化系病研究中心,过敏与免疫相关疾病重点实验室, 武汉 430071, 湖北

收稿日期:2005-09-24 修回日期:2005-10-31 出版日期:2005-12-26 发布日期:2020-11-11
作者简介:张林,男,硕士研究生,研究方向:炎症性肠病。Tel:13036139553E-mail:zhanglin116@sina.com
基金资助:
湖北省科技攻关资助项目(No2003AA301C08)

Effect of 5-aminosalicylic acid on antioxidant mechanism and attenuation of proinflammatory cytokines in trinitrobenzene sulfonic acid-induced coli-tis in rats

ZHANG Lin, XIA Bing, CHENG Hong

Department of Internal Medicine,Zhongnan Hospital,Wuhan University School of Medicine,Wuhan 430071,China

Received:2005-09-24 Revised:2005-10-31 Online:2005-12-26 Published:2020-11-11

摘要/Abstract

摘要： 目的: 探讨5-氨基水杨酸(5-ASA) 灌肠治疗对三硝基苯磺酸(TNBS) 诱导大鼠结肠炎的抗氧化作用及对细胞因子表达的影响。方法: 建立 TNBS 结肠炎模型,给予 5-ASA 灌肠治疗,同时设正常对照组和模型组。于治疗后 1、2 周,评价结肠大体、组织学损伤及髓过氧化物酶(MPO) 活性,检测超氧化物歧化酶(SOD) 活性、丙二醛(MDA) 水平,逆转录-多聚酶链反应(RT-PCR) 检测结肠组织白细胞介素(IL)-1β和肿瘤坏死因子(TNF)-αmRNA 表达水平。结果: 5-ASA 灌肠治疗能明显降低结肠炎大鼠的大体、组织学评分及MPO 活性(P<0.05),升高SOD 活性(P<0.05),降低 MDA 水平(P<0.05),降低 IL-1β和TNF-α表达水平(P<0.05) 。结论: 5-ASA 灌肠治疗TNBS 诱导的大鼠结肠炎疗效显著,其机制与抗氧化作用及抑制 IL-1β和 TNF-α的表达有关。

关键词: 5-氨基水杨酸, TNBS 诱导的结肠炎, 超氧化物歧化酶, 丙二醛, 白细胞介素-1β, 肿瘤坏死因子-α

Abstract: AIM: To investigate the effect and mech-anism of 5-aminosalicylic acid (5-ASA) in topical treat-ment on trinitrobenzene sulfonic acid (TNBS)-induced co-litis in rats.METHODS: Colitis wasinduced by intraco-lonic administration of TNBS and was treated with 5-ASA at the dose of 100 mg·kg^-1 for2 weeks.Normal control grouPwas administrated with normal saline and TNBS control grouPwas treated with TNBS,not with 5-ASA.Macroscopic damage,histological changes and myeloper-oxidase (MPO) activity were evaluated.Superoxide dis-mutase (SOD) activity and malondialdehyde (MDA) level in colonic mucosa were detected by kits.The expression of interleukin-1β(IL-1β) and tumornecrosis factor-α(TNF-α) mRNAs in colonic mucosa was determined by a reverse transcription and polymerase chain reaction meth-od.RESULTS: Compared with TNBS control group,the macroscopic and histological changes and MPO activity in 5-ASA treated groups were improved.SOD activity was increased and the level of MDA in colonic mucosa was re-duced significantly.The expression of IL-1βand TNF-mRNAs in colonic mucosa was also decreased significant-ly.CONCLUSION: 5-ASA enema can significantly ameliorate TNBS-induced colitis in rats via antioxidant mechanism and attenuation of proinflammatory cytokine expression.

Key words: 5-aminosalicylic acid, TNBS induced colitis, superoxide dismutase, malondialdehyde, interleu-kin-1β, tumornecrosis factor-α

中图分类号:

R965.1

张林, 夏冰, 程虹. 5-氨基水杨酸治疗结肠炎的抗氧化作用及对细胞因子表达的影响[J]. 中国临床药理学与治疗学, 2005, 10(12): 1344-1348.

ZHANG Lin, XIA Bing, CHENG Hong. Effect of 5-aminosalicylic acid on antioxidant mechanism and attenuation of proinflammatory cytokines in trinitrobenzene sulfonic acid-induced coli-tis in rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2005, 10(12): 1344-1348.

参考文献

1 Mckenzie SM,Doe WF,Buffinton GD.5-aminosalicylic acid prevents oxidant mediated damage of glyceraldehyde-3-phos-phate dehydrogenase in colon epithelial cells[J].Gut,1999;44:180-5
2 Simmonds NJ,MillarAD,Blake BR,Rampton DS.Antioxidant effects of aminosalicylates and potential new drugs forinflamma-tory bowel disease:assessment in cell-free systems an inflamed human colorectal biopsies[J].Aliment Pharmacol Ther,1999;13:363-72
3 Nielsen O,Buhave K,Elmgreen J,Ahnfelt-Ronne I.Inhibition of 5-lipoxygenase pathway of arachidonic acid metabolism in hu-man neutrophils by sulfasalazine and 5-aminosalicylic acid[J].Dig Dis Sci,1987;32:577-82
4 Hawkey C,Boughton-Smith N,Whittle B.Modulation of human colonic arachidonic acid metabolism by sulfasalazine[J].Dig Dis Sci,1985;30:1161-5
5 Nikolaus S,Folsch UR,SchreiberS.Immunopharmacology of 5-aminosalicylic acid and of glucocorticoids in the therapy of in-flammatory bowel disease[J].Hepatogastroenterology,2000;47:71-82
6 Rousseaux C,Lefebvre B,Dubuquoy L,Lefebvre P,Romano O,Auwerx J,et al.Intestinal antiinflammatory effect of 5-aminosal-icylic acid is dependent on peroxisome proliferator-activated re-ceptor-gamma[J].J ExpMed,2005;201:1205-15
7 Van Staa TP,Card TR,Leufkens FG,Logan RF.5-aminosalicy-late use and colorectal cancerrisk in inflammatory bowel dis-ease:a large epidemiological study[J].Gut,2005;54:1573-8
8 Morris GP,Beck,PL,Herridge,MS,Depew,WT,Szewc-zuk,MR,Wallace,JL.Hapten-induced model of chronic in-flammation and ulceration in the rat colon[J].Gastroenterology,1989;96:795-803
9 Bobin-Dubigeon C,Collin X,GrimaudN,Robert JM,Le Baut G,Petit JY.Effectsof tumornecrosisfactor-αsynthesisinhibitors on rat trinitrobenzene sulphonic acid-induced chronic colitis[J].EurJ Pharmacol,2001;42:103-10
10 Macpherson BR,PfeifferCJ.Experimental production of diffuse colitis in rats[J].Digestion,1978;17:135-50
11 Marshall JK,Irvine EJ.Putting rectal 5-aminosalicylic acid in its place:the role in distal ulcerative colitis[J].Am J Gastroen-terol,2000;95:1628-36
12 DeVosM,Verdievel H,Schoonjas R,PraetM,BogaertM,Barbi-erF.Concentration of 5-ASA and Ac-5-ASA in human ileoco-lonic biopsy homogenatesafteroral5-ASA preparations[J].Gut,1992;33:1338-42
13 SafdiM,DeMicco M,Sninsky C,Banks P,Wruble L,Deren J,et al.A double-blind comparison of oral versus rectal me-salamine versus combination therapy in the treatment of distal ulcerative colitis[J].Am J Gastroenterol,1997;92:1867-71
14 McPhee MS,Swan JT,Biddle WL,Greemberg NJ.Proctocolitis unresponsive to conventional therapy response to 5-aminosalicyl-ic acid enemas[J].Dig Dis Sci,1987;32:76-81
15 Biddle WL,MinerBP.Long-term use of mesalazine enemas to induce remission in ulcerative colitis[J].Gastroenterology,1990;99:113-8
16 Egan LJ,Mays DC,Huntoon CJ,Bell MP,Pike MG,Sandborn WJ,et al.Inhibition of interleukin-1-stimulated NF-kappaB Re-lA p65 phosphorylation by mesalamine is accompanied by de-creased transcriptional activity[J].J Biol Chem,1999;274:26448-53
17 KaiserGC,Yan F,Polk DB.Mesalamine blocks tumornecro-sis factorgrowth inhibition and nuclearfactorkappaB activation in mouse colonocytes[J].Gastroenterology,1999;116:602-9
18 Elson CO,BalfourR,SartorG,Tennyson S,Robert H,Ridded L.Experimental models of inflammatory bowel disease[J].Gas-troenterology,1995;109:1344-67
19 Lih-Brody L,Powell SR,CollierKP,Reddy GM,Cerchia R,Kahn E,et al.Increased oxidative stress and decreased antioxi-dant defenses in mucosa of inflammatory bowel disease[J].Dig Dis Sci,1996;41:2078-86
20 KruidenierL,Verspaget HW.Review article:oxidative stress as a pathogenic factorin inflammatory bowel disease-radicals orri-diculous[J] ?Aliment Pharmacol Ther,2002;16:1997-2015
21 SiesH.Oxidative stress:from basic research to clinical applica-tion[J].Am J Med,1991;91:31-7
22 Xia B,Deng CS,Chen DJ,Zhou Y,Xiao JQ.Role of copperzinc superoxide dismutase in the short trem treatment of acetic acid-induced colitis in rats[J].Acta Gastroent Latinoamer,1996;26:227-30
23 Yagi K.Lipid peroxide and human disease[J].Chem phys Lip-id,1987;45:337-51
24 Gionchetti P,Guarnieri C,Campieri M,Belluzzi A,Brignola C,Oannone P,et al.Scavengereffect of sulfasalazine,5-amin-osalicylic acid and olsalazine on superoxide radical generation[J].Dig Dis Sci,1991;36:174-8
25 RoglerG,Andus T.Cytokines in inflammatory bowel disease[J].World J Surg,1998;22:382-9

[1]	王艳红, 蒲君峰, 李红玲, 冯铁新. 锰超氧化物歧化酶模拟物对三硝基苯磺酸诱导溃疡性结肠炎大鼠的保护作用及机制研究[J]. 中国临床药理学与治疗学, 2020, 25(10): 1081-1087.
[2]	于瀚，钟相根，李耘州，许宗颖，石少华，邓秀兰. 褪黑素对肝内胆汁淤积大鼠肝组织NO、MDA、GSH及NADPH的影响[J]. 中国临床药理学与治疗学, 2019, 24(11): 1221-1226.
[3]	王艳红，冯铁新，蒲君峰，张玲芳，李红玲. 锰超氧化物歧化酶模拟物对四氯化碳致小鼠急性肝损伤的保护作用[J]. 中国临床药理学与治疗学, 2018, 23(11): 1209-1214.
[4]	徐慧，张民远，戴勤学. miR-145通过调节SOD活性介导人参皂苷Rb1对脑缺血再灌注损伤大鼠的脑保护作用[J]. 中国临床药理学与治疗学, 2018, 23(11): 1215-1220.
[5]	樊开宇，王冰，梅骁乐，陈志武. 滁菊总黄酮对大鼠脑缺血再灌注损伤的保护作用[J]. 中国临床药理学与治疗学, 2017, 22(1): 9-12.
[6]	汪婷婷，蔡标，王艳，吴倩，蔡润泽，刘长安. 染料木素对阿尔茨海默病模型大鼠氧化应激和Bcl-2的影响[J]. 中国临床药理学与治疗学, 2016, 21(12): 1335-1340.
[7]	肖洪玲，龙子江，陈明，施慧，方海雁. 压疮灵对压疮模型大鼠局部病理改变和血清SOD、MDA、EGF和IL-6含量的影响[J]. 中国临床药理学与治疗学, 2016, 21(1): 23-27.
[8]	邵美琴, 陈海娥, 何金波, 马迎春, 黄林静, 陈丹, 汪洋, 王万铁. JNK在缺血后处理减轻再灌注损伤肺细胞凋亡中的作用[J]. 中国临床药理学与治疗学, 2015, 20(5): 531-536.
[9]	王静, 王海华, 姜玉新, 周萍萍, 王建安. 金叶女贞果实花青素的镇痛作用初探[J]. 中国临床药理学与治疗学, 2015, 20(1): 38-42.
[10]	邹柳义, 王美荣, 倪连松. 酮替芬对高糖高脂饮食大鼠胰岛素抵抗的干预研究[J]. 中国临床药理学与治疗学, 2014, 19(7): 761-765.
[11]	阎紫菲, 岑彦艳, 李小丽, 匡梅, 曹冠群, 李攀, 周红. 青蒿琥酯对雨蛙素联合脂多糖致急性胰腺炎模型小鼠的治疗作用[J]. 中国临床药理学与治疗学, 2014, 19(4): 361-365.
[12]	马玉红, 姚海, 王欢, 杨解人. 原花青素对D半乳糖联合AlCl₃诱导的阿尔茨海默病大鼠海马Aβ、tau和SOD的影响[J]. 中国临床药理学与治疗学, 2014, 19(3): 280-283.
[13]	金婉冰. 葛根素对庆大霉素致大鼠肾毒性的保护作用[J]. 中国临床药理学与治疗学, 2013, 18(8): 864-867.
[14]	李金纯, 韦红, 王小玲, 郝静梅, 魏小娣. 姜黄素对新生鼠坏死性小肠结肠炎模型的抗氧化作用及机制[J]. 中国临床药理学与治疗学, 2013, 18(1): 17-23.
[15]	张晓溪, 郑晗, 马战胜, 史璐行, 曾水林. 红景天对睡眠剥夺大鼠学习记忆的影响及其机制探索[J]. 中国临床药理学与治疗学, 2012, 17(6): 634-638.