组织相关巨噬素3保护肺血管内皮糖萼治疗急性呼吸窘迫综合征的机制研究  

Mechanism of Maresin conjugates in tissue regeneration 3 protecting pulmonary vascular endothelial glycocalyx in acute respiratory distress syndrome

作　　者：江雅婷 刘林峰 沈辰曦 陈奔 刘婷[1] 龚裕强[1] Yating Jiang;Linfeng Liu;Chenxi Shen;Ben Chen;Ting Liu;Yuqiang Gong(Department of Intensive Medicine,the Second Affiliated Hospital of Wenzhou Medical University,Wenzhou 325000,China;Department of Anesthesia and Perioperative Medicine,the Second Affiliated Hospital of Wenzhou Medical University,Wenzhou 325000,China)

机构地区：[1]温州医科大学附属第二医院重症医学科,浙江温州325000 [2]温州医科大学附属第二医院麻醉与围术期医学科,浙江温州325000

出　　处：《中华危重症医学杂志(电子版)》2024年第5期353-362,共10页Chinese Journal of Critical Care Medicine:Electronic Edition

基　　金：国家自然科学基金项目(82300072);浙江省自然科学基金项目(LY19H150002);温州市基础性科研项目(Y20210094)。

摘　　要：目的探讨组织相关巨噬素3(MCTR3)对脂多糖(LPS)诱导的急性呼吸窘迫综合征(ARDS)小鼠肺血管内皮糖萼降解的保护作用及机制。方法将120只C57BL/6小鼠分为对照组、LPS组、LPS+MCTR3组和MCTR3组,每组各30只。对照组和MCTR3组小鼠气管内给予等渗NaCl溶液(50μL),LPS组和LPS+MCTR3组小鼠气管内给予LPS(1 mg/kg,溶于50μL等渗NaCl溶液中)建立ARDS模型,LPS+MCTR3组和MCTR3组同时尾静脉注射MCTR3(8 mg/kg),4组均为6 h后取材。观察各组小鼠临床预后以及相关病理改变,电镜观察肺血管内皮糖萼及肺泡上皮细胞线粒体结构变化。结果气管内给予等渗NaCl溶液后4 d,对照组与MCTR3组无小鼠死亡,而LPS组仅1只小鼠存活,LPS+MCTR3组4只存活。4组小鼠4 d生存情况比较,差异有统计学意义(χ^(2)=22.810,P<0.001),且LPS组小鼠4 d生存情况较对照组和MCTR3组均明显下降;LPS+MCTR3组小鼠4 d生存情况显著优于LPS组(P均<0.001)。4组小鼠的动脉血氧分压(PaO2)、氧合指数、肺损伤评分、肺组织湿/干重(W/D)比、肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)、内皮糖萼脱落产物硫酸乙酰肝素蛋白多糖2(HSPG2)、多配体蛋白聚糖1(SDC-1),肺血管内皮糖萼降解标志物乙酰肝素酶(HPA)、内皮糖萼相关蛋白SDC-1以及线粒体相关蛋白抗沉默信息调节因子1(SIRT1)、过氧化物酶体增殖物激活受体γ共激活因子1α(PGC-1α)、核呼吸因子1(NRF1)、NRF2、线粒体转录因子A(TFAM)和Flameng评分比较,差异均有统计学意义(F=8.812、21.470、123.451、148.994、57.906、92.948、47.971、88.109、26.839、31.928、12.444、5.537、9.865、12.423、16.352、294.910,P均<0.001)。且LPS+MCTR3组PaO2、氧合指数、SDC-1、SIRT1、PGC-1α、NRF1、NRF2、TFAM蛋白均较LPS组显著升高,肺损伤评分、肺组织W/D比、TNF-α、IL-1β、HSPG2、SDC-1、HPA蛋白和Flameng评分均显著降低(P均<0.05)。结论MCTR3可以改善ARDS小鼠的临床预后、病理变化,促进�Objective To investigate the protective effects and mechanisms of Maresin conjugates in tissue regeneration 3(MCTR3)on the degradation of pulmonary vascular endothelial glycocalyx in mice with lipopolysaccharide(LPS)-induced acute respiratory distress syndrome(ARDS).Methods A total of 120 C57BL/6 mice were divided into four groups according to a random number table:a Control group,a LPS group,a LPS+MCTR3 group,and a MCTR3 group,with 30 mice in each group.The Control and MCTR3 groups received intratracheal administration of isotonic NaCl solution(50μL),while the LPS and LPS+MCTR3 groups intratracheally received LPS(1 mg/kg in 50μL saline)to establish a ARDS model.Additionally,the LPS+MCTR3 and MCTR3 groups intravenously received MCTR3(8 mg/kg).All groups were sampled 6 hours later.The clinical prognosis and related pathological changes were observed in each group.Electron microscopy was used to observe the structure of pulmonary vascular endothelial glycocalyx and alveolar epithelial cell mitochondria.Results After administering isotonic NaCl solution intratracheally for 4 days,there were no deaths in the Control and MCTR3 groups,whereas only one mouse survived in the LPS group,and four mice survived in the LPS+MCTR3 group.The difference in 4-d survival among the groups was statistically significant(χ^(2)=22.810,P<0.001).Moreover,the 4-d survival of mice in the LPS group was significantly decreased compared with the Control and MCTR3 groups;the 4-d survival of mice in the LPS+MCTR3 group was significantly better than that of the LPS group(all P<0.001).The arterial partial pressure of oxygen(PaO2),oxygenation index,pathological injury scores,lung tissue wet/dry weight(W/D)ratio,tumor necrosis factor-alpha(TNF-α),interleukin-1 beta(IL-1β),endothelial glycocalyx degradation products of heparan sulfate proteoglycan 2(HSPG2)and syndecan-1(SDC-1),glycocalyx degradation marker heparanase(HPA),endothelial glycocalyx-related protein SDC-1,mitochondrial-associated proteins of Sirtuin 1(SIRT1),peroxisome proliferator-ac

关 键 词：组织相关巨噬素3 急性呼吸窘迫综合征 内皮糖萼 线粒体功能 

分 类 号：R28[医药卫生—中药学]