基于p38 MARK/MMP-9信号通路探讨自拟复方愈溃汤对UC大鼠肠道炎症、氧化应激及屏障功能的影响  

Exploration of Effects of Compound Yukui Decoction on Intestinal Inflammation,Oxidative Stress and Barrier Function in UC Rats Based on p38 MARK/MMP-9 Signaling Pathway

作　　者：袁翠 雷晓红[2] 莫黎[2] YUAN Cui;LEI Xiaohong;MO Li(Endoscopy Center,the Second Affiliated Hospital of Hunan University of Chinese Medicine,Changsha 410005,China;Department Five of Anorectal Medicine,the Second Affiliated Hospital of Hunan University of Chinese Medicine,Changsha 410005,China)

机构地区：[1]湖南中医药大学第二附属医院内镜中心,长沙410005 [2]湖南中医药大学第二附属医院肛肠五科,长沙410005

出　　处：《医学综述》2023年第14期2891-2896,2902,共7页Medical Recapitulate

基　　金：湖南省自然科学基金(S2021JJMSXM1511)。

摘　　要：目的探讨自拟复方愈溃汤通过p38促分裂原活化的蛋白激酶(MAPK)/基质金属蛋白酶9(MMP-9)通路对溃疡性结肠炎(UC)大鼠肠道炎症、氧化应激及屏障功能的影响。方法选取雄性Wistar大鼠75只,采用随机数字表法分为对照组、模型组、低、中、高剂量汤药组,每组15只。除对照组外,其余各组均以2,4,6-三硝基苯磺酸/乙醇致炎法建立UC大鼠模型。其中,对照组和模型组以0.9%氯化钠溶液灌胃,低、中、高剂量汤药组分别以自拟复方愈溃汤4.2 g/(kg·d)、8.4 g/(kg·d)、16.8 g/(kg·d)灌胃。比较各组大鼠的一般情况,结肠组织疾病活动指数(DAI)评分和组织病理评分、炎症因子[肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和γ干扰素(INF-γ)]、氧化应激指标[超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽(GSH)]、肠黏膜屏障功能蛋白[闭锁蛋白(Occludin)、闭锁小带蛋白-1(ZO-1)]及p-p38 MAPK/p38 MAPK、MMP-9蛋白表达的变化。结果低、中、高剂量汤药组DAI评分和组织病理评分均低于模型组[(2.55±0.50)分、(1.50±0.32)分、(0.82±0.25)分比(3.25±0.65)分,(5.15±1.14)分、(3.00±0.78)分、(2.00±0.65)分比(6.33±1.30)分],且低、中、高剂量汤药组DAI评分和组织病理评分呈剂量依赖性降低趋势(P<0.05)。低、中、高剂量汤药组TNF-α、IL-6、IFN-γ水平均低于模型组,且低、中、高剂量汤药组TNF-α、IL-6、IFN-γ水平呈剂量依赖性降低趋势(P<0.05)。低、中、高剂量汤药组SOD、GSH水平均高于模型组,MDA水平均低于模型组;且低、中、高剂量汤药组SOD、GSH水平呈剂量依赖性升高趋势,MDA水平呈剂量依赖性降低趋势(P<0.05)。低、中、高剂量汤药组Occludin、ZO-1表达均高于模型组,p-p38 MAPK/p38 MAPK与MMP-9表达均低于模型组;且低、中、高剂量汤药组Occludin、ZO-1表达呈剂量依赖性升高趋势,p-p38 MAPK/p38 MAPK与MMP-9表达呈剂量依赖性降低趋势(P<0.05)。结论自拟复方Objective To investigate the effect of compound Yukui decoction on intestinal inflammation,oxidative stress and barrier function in ulcerative colitis(UC)rats via the p38 mitogen-activated protein kinase(MAPK)/matrix metalloproteinase-9(MMP-9)pathway.Methods A total of 75 male Wistar rats were selected and divided into a control group,a model group,a low,a medium and a high dose decoction group by random number table method,with 15 rats in each group.Except for the control group,all the other groups established UC rat models using 2,4,6-trinitro-benzene-sulfonic acid/ethanol induced inflammation method.The control group and the model group were given intragastric administration of 0.9%sodium chloride solution.The low,medium and high dosedecoction groups were gavaged with self-made compound Yukui decoction 4.2 g/(kg·d),8.4 g/(kg·d)and 16.8 g/(kg·d),respectively.The general condition,disease activity index(DAI)score and histopathological score,the expression of inflammatory factors[tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),interferon-γ(INF-γ)],oxidative stress indicators[superoxide dismutase(SOD),malondialdehyde(MDA),glutathione(GSH)],colonic mucosal barrier function proteins[occludin,zonula occluden-1(ZO-1)]and p-p38 MAPK/p38 MAPK and MMP-9 proteins expression changes of each group were compared.Results The DAI score and histopathological score of the low,medium,and high dose decoction groups were lower than those of the model group(2.55±0.50,1.50±0.32,0.82±0.25 vs 3.25±0.65,5.15±1.14,3.00±0.78,2.00±0.65 vs 6.33±1.30),and the DAI score and histopathological score of the low,medium,and high-dose decoction groups showed a dose-dependent decreasing trend(P<0.05).The levels of TNF-α,IL-6,IFN-γin the low,medium,and high dose decoction groups are all lower than the model group,and the levels of TNF-α,IL-6,IFN-γin the low,medium,and high dose decoction groups showed a dose-dependent decreasing trend(P<0.05).The levels of SOD and GSH in the low,medium,and high dose decoction groups were higher

关 键 词：溃疡性结肠炎 自拟复方愈溃汤 p38促分裂原活化的蛋白激酶 基质金属蛋白酶9 氧化应激 

分 类 号：R574.62[医药卫生—消化系统]