麦冬多糖通过Nrf2/HO-1信号通路对肺缺血再灌注损伤大鼠肺组织的保护作用  

Protective effects of ophiopogon polysaccharides via Nrf2/HO-1 pathway on lung ischemia-reperfusion injury rats

作　　者：汪洋 张辉[1] 马东波[1] 邓翔[1] 伍冬冬 吴秋歌[1] WANG Yang;ZHANG Hui;MA Dongbo;DENG Xiang;WU Dongdong;WU Qiuge(Department of Respiratory and Critical Care Medicine,the First Affiliated Hospital,Zhengzhou University,Zhengzhou 450052)

机构地区：[1]郑州大学第一附属医院呼吸与危重医学科,郑州450052

出　　处：《郑州大学学报（医学版）》2023年第4期464-468,共5页Journal of Zhengzhou University(Medical Sciences)

基　　金：国家自然科学基金项目(82100093);河南省医学科技攻关省部共建重点项目(SBGJ202102166);郑州大学第一附属医院青年基金项目(YNQN2017050)。

摘　　要：目的:探讨麦冬多糖(OP)对肺缺血再灌注损伤(LIRI)大鼠肺组织的保护作用。方法:60只SD雄性大鼠随机分为假手术组,LIRI组,OP低、中、高剂量组,OP高剂量+核因子E2相关因子2(Nrf2)抑制剂ML385组(OM组),每组10只。OP低、中、高剂量组造模前分别给予50、100、200 mg/kg OP连续灌胃14 d,假手术组和LIRI组给予等体积生理盐水灌胃,OM组在高剂量OP处理基础上,于造模前1 h腹腔注射30 mg/kg ML385。除假手术组外其余各组采用夹闭左肺门法建立大鼠LIRI模型。缺血再灌注120 min后处死大鼠,计算各组大鼠肺组织湿/干质量比,检测血浆中超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量,ELISA法检测肺组织中白介素(IL)-1β、IL-6、肿瘤坏死因子-α(TNF-α)、 Nrf2、血红素加氧酶1(HO-1)水平,实时荧光定量PCR法检测Nrf2、HO-1 mRNA的表达。结果:与假手术组相比,LIRI组大鼠肺组织湿/干质量比升高(P<0.05);血浆中SOD活性降低、MDA含量升高(P<0.05);肺组织中IL-1β、IL-6、TNF-α水平升高(P<0.05);肺组织Nrf2、HO-1蛋白和mRNA的表达升高(P<0.05)。OP可逆转LIRI大鼠以上指标的变化,且有一定的剂量依赖性(P<0.05)。与OP高剂量组相比,OM组大鼠肺组织湿/干质量比升高(P<0.05);血浆中SOD活性降低、MDA含量升高(P<0.05);肺组织中IL-1β、IL-6、TNF-α水平升高(P<0.05);肺组织Nrf2、HO-1蛋白和mRNA的表达降低(P<0.05)。结论:OP对LIRI大鼠肺组织有一定的保护作用,该作用可能与激活Nrf2/HO-1信号通路有关。Aim:To study the protective effects of ophiopogon polysaccharide(OP)on lung ischemia-reperfusion injury(LIRI)rats.Methods:A total of 60 SD male rats were randomly divided into 6 groups,sham operation group,LIRI group,OP low,middle,high dose groups,OP high dose+Nrf2 inhibitor ML385(OM)group,with 10 rats in each group.Before modeling,the rats in low,medium,and high dose groups were given 50,100,200 mg/kg OP by continuous gavage for 14 days.The rats in sham operation group and LIRI group were given equal volume of normal saline by gavage.On the basis of high dose OP treatment,the rats in OM group were intraperitoneally injected with 30 mg/kg ML3851 hour before modeling.Except the sham operation group,the left hilus pulmonis of rats in the other 5 groups was clamped to establish a rat LIRI model.After 120 min reperfusion,the wet/dry mass ratio of the lung tissue was calculated,and the activity of SOD and the content of MDA in plasma were determined.The levels of interleukin(IL)-1β,IL-6,tumor necrosis factor-α(TNF-α),nuclear factor E2 related factor 2(Nrf2)and heme oxidase 1(HO-1)were detected by ELISA.The mRNA expressions of Nrf2 and HO-1 were measured by real-time fluorescent quantitative PCR.Results:Compared with the sham operation group,the wet/dry mass ratio of lung tissue in the LIRI group increased(P<0.05);SOD activity reduced and MDA content increased in plasma(P<0.05);the contents of IL-1β,IL-6,and TNF-αin lung tissue increased(P<0.05);the protein and mRNA expressions of Nrf2 and HO-1 increased(P<0.05).OP could reverse the changes in the above indicators in LIRI rats,and there was a certain dose dependence(P<0.05).Compared with the OP high dose group,the wet/dry mass ratio of lung tissue in the OM group increased(P<0.05);SOD activity reduced and MDA content increased in lung tissue(P<0.05);the levels of IL-1β,IL-6,and TNF-αin lung tissue increased(P<0.05);the protein and mRNA expressions of Nrf2 and HO-1 decreased(P<0.05).Conclusion:OP has certain protective effects on LIRI rats,which may be related to

关 键 词：麦冬多糖 肺缺血再灌注 Nrf2/HO-1信号通路 氧化应激 大鼠 

分 类 号：R563.9[医药卫生—呼吸系统]