依托咪酯对DNBS诱导的大鼠溃疡性结肠炎氧化应激和炎症因子表达的干预及机制研究  

Intervention mechanism of etomidate on DNBS-induced oxidative stress and inflammatory factor expression in ulcerative colitis in rats

作　　者：李曦 吴仲 代丽娜 李仕梅 王子明 许凌懿 孔航[3] LI Xi;WU Zhong;DAI Li-Na;LI Shi-Mei;WANG Zi-Ming;XU Ling-Yi;KONG Hang(Department of Anesthesiology,the First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine,Guiyang 550001,China)

机构地区：[1]贵州中医药大学第一附属医院麻醉科,贵阳550001 [2]贵州中医药大学第一附属医院肛肠科,贵阳550001 [3]贵州省贵阳市第一人民医院麻醉科,贵阳550002

出　　处：《中国免疫学杂志》2021年第23期2822-2826,2831,共6页Chinese Journal of Immunology

基　　金：贵州省中医药管理局中医药、民族医药科学技术研究课题(QZYY-2019-009)。

摘　　要：目的:本文旨在探究依托咪酯(Eto)对2,4-二硝基苯磺酸(DNBS)诱导的大鼠溃疡性结肠炎(UC)的保护作用及相关机制。方法:将40只SPF级Wistar大鼠随机分为5组,对照组、模型组、依托咪酯低剂量组(1.5 mg/kg)、中剂量组(3 mg/kg)、高剂量组(6 mg/kg)。采用DNBS诱导法构建溃疡性结肠炎大鼠模型,观察记录病变活动指数(DAI)和结肠黏膜损伤指数(CMDI)。HE染色观察结肠组织病理状态并进行结肠组织学评分(HS)。TUNEL染色检测细胞凋亡,Western blot检测Bax和Bcl-2的表达。试剂盒检测超氧化物歧化酶(SOD)、丙二醛(MDA)水平,ELISA检测IL-1β、IL-6、TNF-α表达水平,Western blot检测p-P65的表达。结果:与对照组相比,DNBS诱导组DAI指数、CMDI指数和HS评分显著增加(P<0.05),出现结肠水肿溃烂,大面积溃疡灶,大量炎症细胞浸润等UC的组织病理学改变,UC大鼠模型构建成功。UC大鼠结肠组织细胞凋亡率及Bax/Bcl-2显著上调(P<0.05),SOD水平明显下调,MDA水平明显上调(P<0.05),IL-1β、IL-6、TNF-α炎症因子水平及NF-κB p-P65水平显著上调(P<0.05)。与模型组相比,Eto中、高剂量组DAI指数、CMDI指数和HS评分显著降低(P<0.05),且病理学改变明显减轻,Eto中、高剂量组呈剂量依赖性显著下调细胞凋亡率及Bax/Bcl-2(P<0.05),上调SOD水平,下调MDA水平(P<0.05),IL-1β、IL-6、TNF-α炎症因子水平及NF-κB p-P65水平显著下调(P<0.05),Eto低剂量组差异无统计学意义。结论:Eto对DNBS诱导的大鼠UC有明显保护作用,其保护机制为抑制氧化应激和炎症反应及细胞凋亡。Objective:The purpose of this article is to investigate the protection effects of etomidate(Eto)on 2,4-dinitrobenzene sulfonic acid(DNBS)-induced ulcerative colitis(UC)in rats and related mechanisms.Methods:Forty SPF Wistar rats were randomly divided into 5 groups:normal group,model group,low-dose etomidate group(1.5 mg/kg),medium-dose group(3 mg/kg),high-dose group(6 mg/kg).The DNBS induction method was used to construct a rat model of ulcerative colitis,the disease activity index(DAI)and colonic mucosal damage index(CMDI)were observed and recorded.HE staining was used to observe the pathological state of the colon tissue and a colon histopathological score(HS)was performed.TUNEL staining was used to detect apoptosis,and Western blot was used to detect the expression of Bax and Bcl-2.The kit was used to detect the levels of superoxide dismutase(SOD)and malondialdehyde(MDA),ELISA to detect the expression levels of IL-1β,IL-6 and TNF-α,and Western blot to detect the expression of p-P65.Results:Compared with the control group,the DAI index,CMDI index and HS score of the DNBS-induced group were significantly increased(P<0.05),histopathology change of ulcerative colitis such as colonic edema ulceration,large-area ulcer foci,and a large number of inflammatory cell infiltration,the UC rat model was successfully constructed.Apoptosis rate and Bax/Bcl-2 ratio in colon tissue of UC rats were significantly increased(P<0.05),SOD level was significantly decreased,MDA level was significantly increased(P<0.05),the levels of IL-1β,IL-6,TNF-αinflammatory factors and NF-κB p-P65 were significantly increased(P<0.05).Compared with the model group,the DAI index,CMDI index and HS score of the Eto medium and high dose groups were significantly reduced(P<0.05),and the pathological changes were significantly reduced.The Eto medium and high dose groups significantly down-regulated apoptosis rate in a dose-dependent manner and Bax/Bcl-2(P<0.05),up-regulated SOD level,down-regulated MDA level(P<0.05),IL-1β,IL-6,TNF-αinflammatory fac

关 键 词：依托咪酯 DNBS 溃疡性结肠炎 氧化应激 炎症 

分 类 号：R541.9[医药卫生—心血管疾病]