MiR-138-5p通过抑制SIRT1表达增强了海水吸入性肺损伤中炎症反应  

MiR⁃138⁃5p enhanced the inflammation in seawater aspiration⁃induced acute lung injury via inhibition the expression of SIRT1

作　　者：张敏龙 金发光 Zhang Minlong;Jin Faguang(Department of Respiratory and Critical Care Medicine,the Eighth Medical Center,PLA General Hospital,Beijing 100091,China;Department of Respiratory,Tangdu Hospital,Air Force Military Medical University,Xi′an 710032,China)

机构地区：[1]解放军总医院第八医学中心呼吸与危重症医学部,北京100091 [2]空军军医大学唐都医院呼吸科,西安710038

出　　处：《中华肺部疾病杂志（电子版）》2023年第6期751-755,共5页Chinese Journal of Lung Diseases(Electronic Edition)

基　　金：解放军总医院第八医学中心国科金配套基金(QN202211004)。

摘　　要：目的观察miR-138-5p在海水吸入性肺损伤(acute lung injury,ALI)中的作用及机制。方法分别构建海水吸入性肺损伤大鼠及大鼠肺血管内皮细胞(rat pulmonary vascular endothelial cells,RPMVECs)细胞模型,分为空白对照组、海水处理组、miR-138-5p antagomir预处理组和antag NC预处理组。观察肺组织湿干比、伊文思蓝法检测肺微血管通透性,用ELISA法检测肺组织及细胞中肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白介素-1β(interleukin-1β,IL-1β)和白介素-6(interleukin-6,IL-6)的含量,western blot检测SIRT1及乙酰化(Acetyl)-核因子-κB(nuclear factor kappa-B,NF-κB)的表达变化,采用双荧光素酶报告基因实验验证SIRT1和miR-138-5p的作用关系。结果海水干预4 h后,大鼠肺组织湿干比及通透性明显增加,组织及细胞中TNF-α、IL-1β和IL-6的含量增高,miR-138-5p表达明显增高,SIRT1表达出现了下降,Acetyl-NF-κB的表达明显升高。而抑制miR-138-5p的表达后,炎症反应得到了明显的减轻,SIRT表达出现了回升,Acetyl-NF-κB的表达出现了下降。结论增加表达的miR-138-5p在海水吸入性肺损伤炎症的发展中起到了关键作用,这种作用是通过调节SIRT1通路形成的。Objective To observe the role and mechanism of miR⁃138⁃5p in seawater aspiration⁃induced acute lung injury(ALI).Methods Rats and rat pulmonary vascular endothelial cells(RPMVECs)seawater aspiration induced ALI models were established and were divided into 4 groups:normal control group,seawater group,miR⁃138⁃5p antagomir group and antag NC pre⁃treated group.W/D ratio and Evans blue were carried out after modeling.The contents of tumor necrosis factor⁃α(TNF⁃α),interleukin⁃1β(IL⁃1β)and interleukin⁃6(IL⁃6)were measured by enzyme linked immunosorbent serologic assay(ELISA)and the expression of SIRT1 and Acetyl⁃nuclear factor kappa⁃B(NF⁃κB)were measured by western blot.Doubleluciferase reporter gene assay was used to verify the functional relationship between SIRT1 and miR⁃138⁃5p.Results After 4 h seawater stimulation,W/D ratio and Evans blue were obvious and the contents of TNF⁃α,IL⁃1βand IL⁃6 were increased.The expression of miR⁃138⁃5p,Acetyl⁃NF⁃κB were increased and SIRT1 expression was inhibited.Inhibition of miR⁃138⁃5p decreased the inflammation,oxidative stress and Acetyl⁃NF⁃κB and increased the expression of SIRT1.Conclusion These results suggest that increased expression of miR⁃138⁃5p was an important cause in seawater⁃induced ALI and this phenomenon was through SIRT1 pathway.

关 键 词：急性肺损伤 海水 SIRT1通路 miR-138-5p 

分 类 号：R563[医药卫生—呼吸系统]