美沙拉嗪对乙醇所致大鼠急性胃溃疡的保护作用及机制探讨  

Protective effects of mesalazine on ethanol induced acute gastric ulcer in rats and its mechanism

作　　者：田华[1] 李晓利[1] 王金叶 黄静[2] TIAN Hua;LI Xiaoli;WANG Jinye;HUANG Jing(Department of Geriatrics,Honghui Hospital Affiliated to Xi'an Jiaotong University,Xi'an 710054,Shanxi Province,China;Department of Clinical Pharmacy,Honghui Hospital Affiliated to Xi'an Jiaotong University,Xi'an 710054,Shanxi Province,China)

机构地区：[1]西安交通大学附属红会医院老年病科,陕西西安710054 [2]西安交通大学附属红会医院临床药学科,陕西西安710054

出　　处：《世界临床药物》2023年第6期547-551,共5页World Clinical Drug

基　　金：陕西省自然科学基础研究项目(2020JQ-962)。

摘　　要：目的 评估美沙拉嗪对乙醇所致大鼠胃溃疡(gastric ulcer,GU)保护作用及机制。方法 雄性SD大鼠随机分为对照组、溃疡组、奥美拉唑+溃疡组及美沙拉嗪+溃疡组,每组10只。通过口服无水乙醇(5 ml/kg)造成大鼠GU。奥美拉唑组和美沙拉嗪组在服用乙醇前1 h分别口服奥美拉唑(20 mg/kg)和美沙拉嗪(50 mg/kg)。乙醇处理后1 h,观察各组大鼠溃疡面积、病理组织学、脂质过氧化和抗氧化酶水平,以及核因子(nuclear factor,NF)-κB活化。结果 美沙拉嗪预处理显著降低无水乙醇诱导的GU、出血、充血及胃黏膜上皮细胞丢失。美沙拉嗪处理降低胃组织中丙二醛水平,增加总谷胱甘肽和超氧化物歧化酶水平;此外,其还提高环氧合酶-1和前列腺素E_(2)(prostaglandin E_(2),PGE_(2))表达水平,并降低NF-κB活化。结论 美沙拉嗪通过防止氧化损伤、刺激PGE_(2)产生和抑制NF-κB激活,在乙醇诱导的急性GU中发挥保护作用。Objective To evaluate the protective effects and mechanism of mesalazine on ethanol induced gastric ulcer(GU)in rats.Methods Male SD rats were randomly divided into control group,ulcer group,omeprazole+ulcer group and mesalazine+ulcer group,with 10 rats in each group.GU was caused by oral administration of absolute ethanol(5 ml/kg)in rats.Omeprazole group and mesalazine group took omeprazole(20 mg/kg)or mesalazine(50 mg/kg)orally one hour before taking ethanol,respectively.One hour after ethanol treatment,the ulcer area,histopathology,lipid peroxidation,antioxidant enzymes and phosphorylation of nuclear factor(NF)-κB were observed.Results Mesalazine pretreatment significantly decreased alcohol-induced GU,hemorrhage,hyperemia,and epithelial cell loss in the gastric mucosa.Mesalazine pretreatment reduced the level of malondialdehyde and increased total glutathione and superoxide dismutase in gastric tissues.In addition,it increased the expression levels of cyclooxygenase-1 and prostaglandin(PG)E_(2),and decreased the phosphorylation of NF-κB.Conclusion Mesalazine could effectively inhibit ethanol induced acute gastric injury by preventing oxidative damage,stimulating PGE_(2) production,and inhibiting NF-κB activation.

关 键 词：美沙拉嗪 胃溃疡 氧化损伤 核因子-ΚB 

分 类 号：R573.1[医药卫生—消化系统]