姜黄提取物调控Nrf2/Keap1通路对脓毒症急性肺损伤大鼠的影响  

Effect of turmeric extract regulating Nrf2/Keap1 pathway on sepsis-induced acute lung injury in rats

作　　者：王舒[1] 李福星[1] 王萌[1] 周仪华[1] 余志宏[1] 龚园其 WANG Shu;LI Fuxing;WANG Meng;ZHOU Yihua;YU Zhihong;GONG Yuanqi(The Second Affiliated Hospital of Nanchang University,Nanchang 330006,China;School of Medicine,Nanchang University,Nanchang 330000,China)

机构地区：[1]南昌大学第二附属医院,南昌330006 [2]南昌大学医学部,南昌330000

出　　处：《中国免疫学杂志》2024年第12期2580-2584,2590,共6页Chinese Journal of Immunology

基　　金：国家自然科学基金(82260374)。

摘　　要：目的:基于Nrf2/Keap1信号通路探讨姜黄素对脓毒症急性肺损伤大鼠的影响。方法:30只大鼠随机分为假手术组、模型组、姜黄素低、中、高剂量组,每组6只,假手术组大鼠取出盲肠暴露后纳回腹腔,其余组构建脓毒症急性肺损伤模型,术后立即给药,连续3 d,戊巴比妥40 mg/kg麻醉后于颈部总动脉血管收集血液及肺泡灌洗液,处死后取肺组织。评价大鼠脓毒症严重程度;检测肺泡灌洗液细胞总数、中性粒细胞数;HE染色观察肺组织病理损伤;比色法检测肺组织SOD、MDA活性;ELISA检测TNF-α、IL-1β、IL-6水平;qRT-PCR检测肺组织Nrf2、Keap1、HO-1 mRNA表达;Western blot检测肺组织Nrf2、Keap1、HO-1蛋白表达。结果:模型组、姜黄素低、中、高剂量组大鼠较假手术组脓毒症严重程度评分升高,细胞总数、中性粒细胞数增加,SOD水平降低,MDA水平升高,TNF-α、IL-1β、IL-6水平升高,Nrf2、HO-1 mRNA及蛋白表达降低,Keap1 mRNA及蛋白表达增加(P<0.05);姜黄素低、中、高剂量组大鼠较模型组脓毒症严重程度评分降低,细胞总数、中性粒细胞数减少,SOD水平升高,MDA水平降低,TNF-α、IL-1β、IL-6水平降低,Nrf2、HO-1 mRNA及蛋白表达增加,Keap1 mRNA及蛋白表达下降,呈剂量依赖性(P<0.05)。结论:姜黄素可改善大鼠脓毒症急性肺损伤,改善肺部病理损伤,保护肺组织,可能通过调控Nrf2/Keap1通路及相关因子表达实现。Objective:To investigate effect of curcumin on sepsis-induced acute lung injury rats based on Nrf2/Keap1 signaling pathway.Methods:Thirty rats were randomly divided into sham operation group,model group,curcumin low,medium and high doses groups,with 6 rats in each group.Rats in sham operation group were exposed by removing cecum and then returned to abdominal cavity,while rest of rats were constructed a model of acute lung injury in sepsis,and drugs were administered immediately after surgery for 3 consecutive days.After anaesthesia with 40 mg/kg pentobarbital,blood and alveolar lavage fluid were collected from common carotid arteries,and lung tissues were taken after death.Severity of sepsis in rats was evaluated;total cell count and neutrophil count of alveolar lavage fluid were detected;HE staining was performed to observe pathological damage of lung tissues;colorimetric method was used to detect SOD and MDA activities of lung tissues;ELISA was used to detect TNF-α,IL-1βand IL-6 levels;qRT-PCR was used to detect Nrf2,Keap1 and HO-1 mRNA expressions in lung tissues;Western blot was used to detect Nrf2,Keap1 and HO-1 protein expressions in lung tissues.Results:Compared with sham operation group,severity scores of sepsis in model group,curcumin low,medium and high doses groups were increased,total number of cells and neutrophil number were increased,SOD level was decreased,MDA level was increased,TNF-α,IL-1βand IL-6 levels were increased,Nrf2,HO-1 mRNA and protein expressions were decreased,Keap1 mRNA and protein expressions were increased(P<0.05);compared with model group,sepsis severity scores of curcumin low,medium and high doses groups were decreased,total number of cells and neutrophil number were decreased,SOD level was increased,MDA level was decreased,TNF-α,IL-1βand IL-6 levels were decreased,Nrf2 and HO-1 mRNA and protein expressions were increased,Keap1 mRNA and protein expressions were decreased in a dose-dependent manner(P<0.05).Conclu⁃sion:Curcumin can improve acute lung injury in rats with s

关 键 词：Nrf2/Keap1通路 姜黄素 脓毒症 急性肺损伤 

分 类 号：R631[医药卫生—外科学]