姜油酮通过激活Nrf2通路减轻LPS诱导的小鼠急性肺损伤  

Zingerone alleviates LPS-induced acute lung injury in mice via Nrf2 pathway

作　　者：杨敏华[1] 姚友杰[2] 王娟[1] YANG Min-hua;YAO You-jie;WANG Juan(Department of Emergency Medicine,The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine/Henan Province Hospital of TCM,Zhengzhou 450000;Department of cardiovascular Medicine,The First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)

机构地区：[1]河南中医药大学第二附属医院/河南省中医院急诊内科,河南郑州450000 [2]郑州大学第一附属医院心内科,河南郑州450052

出　　处：《西安交通大学学报（医学版）》2020年第1期150-156,共7页Journal of Xi’an Jiaotong University（Medical Sciences）

摘　　要：目的探究姜油酮(zingerone)对脂多糖(LPS)诱导的小鼠急性肺损伤(acute lung injury,ALI)的作用机制。方法将小鼠随机分为对照(Control)组、Zingerone组、LPS组和LPS+Zingerone组,腹腔注射姜油酮或生理盐水预处理,2 h后腹腔注射LPS复制小鼠ALI模型。4 h后处死小鼠,收集肺组织和血清,HE染色观察肺组织损伤情况,Tunel染色观察肺组织细胞凋亡情况。ELISA检测白介素-6(interleukin-6,IL-6)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、IL-1β、超氧化物歧化酶(superoxide dismutase,SOD)和丙二醛(malondialdehyde,MDA)的含量,免疫印迹检测红系衍生核因子相关因子2[nuclear factor(erythroid-derived2)-like 2 protein,Nrf2]和血红素氧合酶-1(heme oxygenase-1,HO-1)的蛋白表达。采用Nrf2基因敲除小鼠,重复上述实验。结果与Control组比较,LPS组肺组织损伤明显加重,细胞凋亡率明显升高;与LPS组比较,LPS+Zingerone组肺损伤明显减轻,细胞凋亡率也明显降低;LPS组血清炎症因子IL-6、TNF-α和IL-1β含量及氧化产物MDA含量与Control组比较明显升高,SOD含量明显低于Control组;LPS+Zingerone组血清IL-6、TNF-α、IL-1β和MDA含量与LPS组比较明显降低,SOD含量明显升高;LPS能明显降低Nrf2和HO-1的表达水平,姜油酮能进一步升高模型小鼠Nrf2和HO-1的表达水平;敲除Nrf2后,姜油酮减轻肺损伤的能力降低,降低IL-6、TNF-α、IL-1β和MDA水平及促进SOD分泌的作用减弱。结论姜油酮可通过促进Nrf2通路激活抑制肺组织炎症反应及氧化应激,从而减轻ALI模型小鼠肺损伤。Objective To investigate the effects and mechanisms of zingerone on LPS-induced acute lung injury(ALI)in vivo.Methods The mice were divided into control group,zingerone group,LPS group,and LPS+zingerone group.Each group was injected intraperitoneally with zingeroneor saline.The mice were injected with LPS after zingerone treatment for 2h and then were sacrificed 4h later.We collected the lung tissue and blood of the mice and determined lung injury by HE staining.Tunnel staining was performed for cell apoptosis.The concentrations of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),IL-1β,superoxide dismutase(SOD)and malondialdehyde(MDA)were measured by ELISA assay.And the protein levels of nuclear factor(erythroid-derived2)-like 2 protein(Nrf2)and heme oxygenase-1(HO-1)were measured by immuno-blot method.And the above-mentioned experiments were repeated by using Nrf2 knockout mice.Results Compared with those in control group,the lung injury of mice in LPS group aggravated and cell apoptosis rate was increased significantly.Compared with LPS group,the injury was alleviated and apoptosis rate was decreased markedly.Meanwhile,the concentrations of inflammatory cytokines,including IL-6,TNF-α,IL-1βand MDA,were up-regulated notably compared with the control group,the concentration of SOD was decreased;the concentrations of IL-6,TNF-α,IL-1βand MDA in LPS+zingerone group were decreased while SOD was increased compared with LPS group.In addition,LPS inhibited the expressions of Nrf2 and HO-1,zingerone up-regulated the protein levels of Nrf2 and HO-1.After knockdown of Nrf2 gene,the effects of zingerone on lung injury,inflammation and oxidative stress in the mouse model of LPS-induced acute lung injury were weakened.Conclusion Zingerone alleviates lung injury in mice by inhibiting inflammation and oxidative stress through activating Nrf2 pathway.

关 键 词：急性肺损伤 姜油酮 炎症 氧化应激 

分 类 号：R563.1[医药卫生—呼吸系统]