瑞芬太尼对内毒素诱导的急性肺损伤大鼠氧自由基、炎症因子及肺纤维化的影响  

Effects of remifentanil on oxygen radicals,inflammatory factors and lung fibrosis in endotoxin induced rats with acute lung injury

作　　者：刘宇[1] 李耀 万永灵[1] LIU Yu;LI Yao;WAN Yong-Ling(Department of Anesthesiology,Sichuan People′s Hospital,Chengdu 610031,China)

机构地区：[1]四川省人民医院麻醉科,成都610031

出　　处：《中国免疫学杂志》2020年第9期1086-1090,共5页Chinese Journal of Immunology

基　　金：四川省科技厅课题项目(2019YFS2309)资助。

摘　　要：目的:探究瑞芬太尼对内毒素诱导的急性肺损伤大鼠氧自由基、炎症因子及肺纤维化的影响。方法:选取75只3周龄SD大鼠,随机选取60只制成急性肺损伤(ALI)模型,并分为模型组(Endotoxin)、低剂量瑞芬太尼组(REM 0.2)、中剂量瑞芬太尼组(REM 0.6)和高剂量瑞芬太尼组(REM 1.2),分别以0.2、0.6、1.2μg/(kg·min)的速率静脉输注瑞芬太尼,模型组静脉输注与高剂量实验组等量的0.9%NaCl,另设15只为空白对照组(Control);使用RT-PCR和Western blot检测各组大鼠肺组织Caspase-3的表达;比较各组大鼠肺损伤评分、肺组织W/D值;使用试剂盒检测氧自由基:ROS、SOD、LDH、MDA的含量;使用ELISA法检测炎症因子:TNF-α、IL-6、IL-1β的含量;使用Western blot检测各组大鼠肺组织α-SMA表达水平;使用Masson染色观察纤维化情况。结果:与空白对照组相比,模型组大鼠Caspase-3 mRNA、Caspase-3蛋白表达、肺损伤评分、肺组织W/D值、ROS、LDH、MDA、TNF-α、IL-6、IL-1β、α-SMA表达水平显著升高(P<0.05),SOD水平显著降低(P<0.05);相比模型组,使用瑞芬太尼处理的各组大鼠Caspase-3 mRNA、Caspase-3蛋白表达、肺损伤评分、肺组织W/D值、ROS、LDH、MDA、TNF-α、IL-6、IL-1β、α-SMA表达水平显著降低(P<0.05),SOD水平显著升高(P<0.05),且在本实验剂量范围内呈剂量依赖性。结论:瑞芬太尼可以通过抑制氧化应激反应和炎症反应并抑制肺组织细胞的凋亡,减轻大鼠因内毒素诱导的急性肺损伤。Objective:To investigate the effects of remifentanil(REM) on oxygen radicals,inflammatory factors and lung fibrosis in endotoxin induced rats with acute lung injury(ALI).Methods:75 3-week-old SD rats were enrolled.60 cases of them were randomly selected to make into ALI models.They were divided into model group(Endotoxin),low-dose REM group(REM 0.2),medium-dose REM group(REM 0.6) and high-dose REM group(REM 1.2).The last three groups were intravenously infused with REM at a rate of 0.2,0.6,1.2 μg/(kg·min),respectively.The model group was given intravenous infusion of 0.9% NaCl whose dosage was the same with that in high-dose REM group.The other 15 cases were enrolled as blank control group(Control).The expression of Caspase-3 in lung tissues of each group was detected by RT-PCR and Western blot.The lung injury score and W/D value of lung tissue were compared among all groups.The kit was performed to detect contens of oxygen radicals(ROS,SOD,LDH,MDA).ELISA was performed to detect inflammatory factors(TNF-α,IL-6,IL-1β).Western blot was performed to detect expression level of α-SMA in lung tissues of each group.The fibrosis was observed by Masson staining.Results:Compared with blank control group,expression of Caspase-3 mRNA and Caspase-3 protein,lung injury score,W/D value of lung tissue,levels of ROS,LDH,MDA,TNF-α,IL-6 and IL-1β,α-SMA expression were significantly increased in model group(P<0.05),while SOD level was significantly decreased(P<0.05).Compared with model group,expression of Caspase-3 mRNA and Caspase-3 protein,lung injury score,W/D value of lung tissue,levels of ROS,LDH,MDA,TNF-α,IL-6 and IL-1β,α-SMA expression were significantly decreased in all groups treated with REM(P<0.05),while SOD level was significantly increased(P<0.05),showing dose-dependence within dose range of the experiment.Conclusion:REM can alleviate ALI induced by endotoxin through inhibiting oxidative stress response,inflammation response and apoptosis of lung tissue cells.

关 键 词：急性肺损伤 瑞芬太尼 内毒素 氧自由基 炎症因子 

分 类 号：R332[医药卫生—人体生理学]