罗格列酮治疗脂多糖诱导小鼠急性肺损伤的实验研究  

Experimental study of rosiglitazone in the treatment of lipopolysaccharide-induced acute lung injury in mice

作　　者：王贵佐[1] 陈芬芬 李惟捷[1] 史少剑 刘璐 韩冬 WANG Gui-zuo;CHEN Fen-fen;LI Wei-jie;SHI Shao-jian;LIU Lu;HAN Dong(Shanxi Provincial People's Hospital,Xian 710068,China;不详)

机构地区：[1]陕西省人民医院,西安710068 [2]西安交通大学第二附属医院 [3]华阴市人民医院

出　　处：《内科急危重症杂志》2020年第5期423-426,共4页Journal of Critical Care In Internal Medicine

基　　金：陕西省自然科学基础研究计划项目(No:2020JM-656);陕西省中医药管理局课题资助项目(No:2019-ZZ-JC037)。

摘　　要：目的:探讨激活过氧化物酶体增殖物激活受体γ(PPARγ)对脂多糖(LPS)诱导小鼠急性肺损伤的保护作用及可能的机制。方法:将6~8周的BALB/c小鼠15只随机分成3组,每组5只。对照组小鼠气管内滴注无菌磷酸缓冲盐溶液60μL,作用24 h;LPS模型组小鼠气管内滴注1 mg/m L LPS 60μL,作用24 h;罗格列酮治疗组小鼠在气管内滴注LPS前24 h和0.5 h给予罗格列酮(PPARγ激动剂)灌胃(20 mg/kg)预处理,再气管内滴注1 mg/m L LPS60μL,作用24 h。观察各组小鼠肺组织病理组织学变化,支气管肺泡灌洗液(BALF)中炎症细胞总数及中性粒细胞变化,采用酶联免疫吸附法(ELISA)检测BALF中促炎性细胞因子TNF-α和高迁移率族蛋白-1(HMGB1)的浓度,免疫印迹法(Western Blot)检测肺组织中晚期糖化终产物受体(RAGE)蛋白表达变化。结果:与对照组比较,在LPS诱导的小鼠模型中,组织病理学显示大量炎性细胞浸润,肺组织结构明显被破坏,BALF内细胞总数、中性粒细胞数、促炎性细胞因子TNF-α显著升高(均P<0.01),而采用罗格列酮预处理小鼠明显抑制LPS诱发的上述改变。与对照组比较,LPS模型组小鼠支气管肺泡灌洗液中HMGB1水平明显升高(P<0.01),Western Blot检测肺组织匀浆RAGE的表达明显增加(P<0.05),而罗格列酮预处理小鼠后,LPS诱发的HMGB1/RAGE的上调被显著抑制。结论:激活PPARγ可能通过抑制HMGB1/RAGE信号通路对LPS诱导急性肺损伤/急性呼吸窘迫综合征起保护作用。Objective:To investigate the protective effect and possible mechanism of activation of PPAR-γon lipopolysaccharide(LPS)-induced acute lung injury(ALI)in mice.Methods:Fifteen 6-8-week male BALB/c mice were randomly divided into three groups.The control group was given sterile PBS(60μL)only intratracheally.LPS model group was instilled intratracheally with 60μL of LPS(1 mg/m L)for 24 h.The mice in rosiglitazone-treated group were treated with twice rosiglitazone(30 mg/kg)orally at 24 h and 30 min separately before stimulation with LPS(1 mg/m L,60μL)instilled intratracheally for 24 h.Twenty-four h after administration of LPS,the histopathological changes of lung tissue,and the number of total cells and neutrophils in bronchoalveolar lavage fluid(BALF)in each group were observed.The concentrations of TNF-α and HMGB1 in BALF were measured by ELISA.The expression of RAGE in lung tissue was detected by Western blotting.Results:As compared with the control group,number of inflammatory cells was significantly increased,lung tissue structure was significantly damaged,the total number of cells and neutrophils in BALF increased significantly,and TNF-α level in BALF increased significantly(all P<0.01).It was suggested that rosiglitazone exhibited protective effects on LPS-induced ALI in mice.As compared with the control group,the level of HMGB1 in BALF(P<0.01)and the expression of RAGE in lung tissue(P<0.05)were significantly increased in LPS model group,suggesting that HMGB1/RAGE signaling pathway was involved in the pathogenesis of ALI.However,the up-regulation of HMGB1/RAGE induced by LPS was significantly inhibited by rosiglitazone pretreatment in mice.Conclusions:This study suggests that activation of PPARγ by rosiglitazone protects LPS-induced ALI/ARDS by inhibiting HMGB1/RAGE signaling pathway.

关 键 词：罗格列酮 过氧化物酶体增殖物激活受体Γ 高迁移率族蛋白-1 晚期糖化终产物受体 急性肺损伤 

分 类 号：R563[医药卫生—呼吸系统]