西维来司他激活PPARγ/PGC1α/NRF2信号通路改善急性肺损伤小鼠炎症反应
Sivelestat activates PPARγ/PGC1α/NRF2 signaling pathway to improve inflammatory response in mice with acute lung injury
徐俊 1万冬冬 2陈思1
作者信息
- 1. 南通市海门区人民医院呼吸与危重症医学科,江苏南通 226199
- 2. 南通市海门区人民医院肿瘤内科,江苏南通 226199
- 折叠
摘要
目的 探究西维来司他对小鼠急性肺损伤诱导的线粒体功能障碍及炎症反应的影响及可能机制.方法 30只C57BL/6小鼠随机分为对照组、急性肺损伤组和西维来司他组,每组10只.HE染色观察各组小鼠肺组织病理学改变;试剂盒及荧光显微镜观察各组小鼠ROS水平和线粒体膜电位;ELISA检测各组小鼠支气管肺泡灌洗液TNF-α、IL-1β和IL-6水平;Western blot检测各组小鼠肺组织线粒体和细胞质Drp1蛋白以及Mfn2、PPARγ、PGC1α和NRF2蛋白表达水平.结果 西维来司他处理改善急性肺损伤小鼠肺组织病理损伤,降低肺组织ROS水平,增加肺组织线粒体膜电位,下调肺组织线粒体Drp1蛋白表达并上调肺组织细胞质Drp1蛋白和细胞中Mfn2、PPARγ、PGC1α和NRF2蛋白表达水平,降低支气管肺泡灌洗液TNF-α、IL-1β和IL-6水平.结论 西维来司他改善急性肺损伤诱导的线粒体功能障碍,降低炎症反应并改善肺损伤,其机制可能与激活PPARγ/PGC1α/NRF2信号通路有关.
Abstract
Objective To investigate the effects of sivelestat on mitochondrial dysfunction and inflammatory response induced by acute lung injury in mice and the possible mechanism.Methods Thirty C57BL/6 mice were randomly divided into control group,acute lung injury group and sivelestat group,with 10 mice in each group.The pathological changes of lung tissues were observed by HE staining;the ROS level and mitochondrial membrane potential were observed by kit and fluorescence microscope;the levels of TNF-α,IL-1β and IL-6 in bronchoalveolar lavage fluid were detected by ELISA;the protein expression levels of mitochondrial and cytoplasmic Drp1,Mfn2,PPARγ,pgC1α and NRF2 were detected by Western blot.Results Sivelestat treatment improved the pathological damage of lung tissues in mice with acute lung injury,reduced the ROS level in lung tissues,increased the mitochondrial membrane potential in lung tissues,down-regulated the protein expression of mitochondrial Drp1 in lung tissues and up-regulated the protein expression of cytoplasmic Drp1 in lung tissues and Mfn2,PPARγ,pgC1α and NRF2 in cells,and reduced the levels of TNF-α,IL-1β and IL-6 in bronchoalveolar lavage fluid.Conclusion Sivelestat improves mitochondrial dysfunction,reduces inflammatory response and improves lung injury induced by acute lung injury,and the mechanism may be related to the activation of PPAR-γ/PGC1α/NRF2 signaling pathway.
关键词
急性肺损伤/西维来司他/线粒体功能障碍/炎症反应/PPARγ/PGC1α/NRF2信号通路Key words
acute lung injury/sivelestat/mitochondrial dysfunction/inflammatory response/PPARγ/PGC1α/NRF2 signaling pathway引用本文复制引用
基金项目
南通市卫生健康委科研课题(MSZ2022108)
出版年
2024
NETL
NSTL
万方数据