低氧诱导因子-1α对脓毒症肠黏膜屏障的保护作用  

Protective effect of hypoxia inducible factor-1αon intestinal mucosal barrier in sepsis

作　　者：何锐 滕文彬 姚刘旭 单跃 祝胜美[1] 李玉红 HE Rui;TENG Wenbin;YAO Liuxu;SHAN Yue;ZHU Shengmei;LI Yuhong(Department of Anesthesiology,the First Affiliated Hospital,College of Medicine,Zhejiang University,Hangzhou 310000,Zhejiang,China;Department of Anesthesiology,Shaoxing People's Hospital,Shaoxing 312000,Zhejiang,China;Shulan Hangzhou hospital,Shulan International Medical College,Shuren University,Hangzhou 310004,Zhejiang,China)

机构地区：[1]浙江大学医学院附属第一医院麻醉科,浙江杭州310000 [2]绍兴市人民医院麻醉科,浙江绍兴312000 [3]树人大学树兰国际医学院附属树兰(杭州)医院麻醉科,浙江杭州310004

出　　处：《中国临床药理学与治疗学》2021年第3期264-270,共7页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：浙江省科学技术厅公益项目(LGF19H030011);浙江省医药卫生科技计划项目(2020KY329,2019306157)。

摘　　要：目的:探讨低氧诱导因子-1α(HIF-1α)对脓毒症肠黏膜屏障的影响及机制。方法:SD大鼠随机分4组:假手术组、脓毒症组、脓毒症+HIF-1α刺激剂组(脓毒症+DMOG组)、脓毒症+HIF-1α抑制剂组(脓毒症+Bay87-2243组),每组6只。采用盲肠结扎穿孔(cecal ligation and perforation,CLP)建立脓毒症模型。ELISA检测大鼠血浆炎性标记物IL-1β、IL-6、TNF-α,氧化应激标记物丙二醛(MDA)以及抗氧化因子超氧化物歧化酶(SOD)、过氧化氢酶(CAT)的水平。Western blot检测大鼠肠黏膜HIF-1α表达。HE染色检测肠黏膜病理学损伤。结果:与假手术组相比,脓毒症大鼠炎症因子、氧化应激因子以及HIF-1α显著上调(P<0.05);给予腹腔注射DMOG明显降低脓毒症大鼠血浆IL-1β、IL-6、TNF-α、MDA水平(P<0.05);增加血浆SOD、CAT水平(P<0.05);HIF-1α表达上调(P<0.05),肠黏膜病理损伤减轻,Chiu's评分显著降低(P<0.05)。口服灌胃Bay87-2243则得到相反的结果。结论:HIF-1α对脓毒症肠黏膜损伤具有保护作用,其机制可能与缓解脓毒症炎性反应和抑制氧化应激水平有关。AIM:To investigate the effect and mechanism of hypoxia inducible factor-1αon intestinal mucosal barrier in sepsis.METHODS:SD rats were randomly divided into 4 groups:sham group,sepsis group,sepsis+HIF-1αstimulant(sepsis+DMOG group),sepsis+HIF-1αinhibitor(sepsis+Bay87-2243 group),6 rats in each group.Sepsis model was established by cecal ligation and perforation(CLP).The levels of inflammatory markers IL-1β,IL-6,TNF-α,oxidative stress markers MDA and antioxidant factors SOD and CAT were detected by ELISA and the expression of HIF-1αin intestinal mucosa was detected by Western blot.The pathological damage of intestinal mucosa was detected by HE staining.RESULTS:Inflammatory factors,oxidative stress factors and HIF-1αwere significantly up-regulated in septic rats(P<0.05).The contents of IL-1β,IL-6,TNF-αand MDA in plasma were significantly decreased by intraperitoneal injection of DMOG(P<0.05);the levels of SOD and CAT in plasma were increased(P<0.05),HIF-1αwas up-regulated(P<0.05),and the pathological damage of intestinal mucosa was alleviated,with decreased Chiu's score(P<0.05).Oral administration of Bay87-2243 gave the opposite result.CONCLUSION:HIF-1αhas a protective effect on intestinal mucosal injury in sepsis.The mechanism may be related to the alleviation of inflammatory response and inhibition of oxidative stress.

关 键 词：脓毒症 炎症反应 氧化应激反应 低氧诱导因子1Α 低氧诱导因子1α刺激剂 低氧诱导因子1α抑制剂 

分 类 号：R631[医药卫生—外科学] R965.2[医药卫生—临床医学]