益母草碱调节IRE1α/TXNIP/NLRP3信号通路对急性呼吸窘迫综合征大鼠炎症反应的影响  

Effect of Leonurine on Inflammatory Response in Rats with Acute Respiratory Distress Syndrome by Regulating the IRE1Α/TXNIP/NLRP3 Signaling Pathway

作　　者：王瑞琪 李立[1] Wang Ruiqi;Li Li(Institute of Basic Research in Clinical Medicine,China Academy of Chinese Medical Sciences,Beijing 100700,China)

机构地区：[1]中国中医科学院中医临床基础医学研究所,北京100700

出　　处：《中国中医急症》2024年第9期1529-1534,共6页Journal of Emergency in Traditional Chinese Medicine

基　　金：国家重点研发计划中医药现代化——中医药应对重大新发疫病的防治一体化关键技术研究(2023YFC3503400);中国中医科学院创新团队项目(CI2021B003)。

摘　　要：目的探究益母草碱调节IRE1α/TXNIP/NLRP3信号通路对急性呼吸窘迫综合征(ARDS)大鼠炎症反应的影响。方法将大鼠随机分为空白组、模型组、益母草碱低剂量组、益母草碱高剂量组、联用HY-N2485组(高剂量益母草碱+NLRP3激活剂)。检测大鼠肺功能;血气分析仪检测氧分压(PaO_(2))和二氧化碳分压(PaCO_(2));ELISA法检测肺泡灌洗液白细胞介素-10(IL-10)、白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)水平;检测肺组织干湿比;检测肺组织丙二醛(MDA)含量、超氧化物歧化酶(SOD)和过氧化氢酶(CAT)活性;HE染色观察大鼠肺组织病理形态;Western blotting检测肺组织中IRE1α、TXNIP、NLRP3、Caspase-1、Cleaved Caspase-3蛋白表达。结果与空白组相比,模型组肺组织形态有明显损伤,PEF、FVC和FEV0.3/FVC水平、PaO_(2)、OI水平、肺泡灌洗液IL-10水平、肺组织CAT和SOD活性降低,PaCO_(2)水平、肺泡灌洗液IL-1β、IL-6、TNF-α水平、肺组织病理评分、肺组织MDA含量、IRE1α、TXNIP、NLRP3、Caspase-1、Cleaved Caspase-3蛋白表达水平升高(P<0.05);与模型组相比,益母草碱低、高剂量组大鼠肺组织损伤明显减轻,PEF、FVC和FEV0.3/FVC水平、PaO_(2)、OI水平、肺泡灌洗液IL-10水平、肺组织CAT和SOD活性升高,PaCO_(2)水平、肺泡灌洗液IL-1β、IL-6、TNF-α水平、肺组织病理学评分、肺组织MDA含量、IRE1α、TXNIP、NLRP3、Caspase-1、Cleaved Caspase-3蛋白表达水平降低(P<0.05);HY-N2485可减弱益母草碱对ARDS大鼠的改善作用(P<0.05)。结论益母草碱可降低ARDS大鼠炎症和氧化应激,减轻肺组织损伤,改善肺功能,可能与抑制IRE1α/TXNIP/NLRP3信号通路有关。Objective:To investigate the effect of leonurine on inflammatory response in rats with acute respiratory distress syndrome(ARDS)by regulating the IRE1α/TXNIP/NLRP3 signaling pathway.Methods:Rats were randomly separated into CK group,Model group,leonurine low-dose(L)group,leonurine high-dose(H)group,and leonurine-H+HY-N2485(NLRP3 activator)group.The lung function of rats was tested.Blood gas analyzer was used to detect partial pressure of oxygen(PaO_(2))and partial pressure of carbon dioxide(PaCO_(2)).ELISA was applied to detect the levels of IL-10,IL-6,IL-1β,and TNF-αin alveolar lavage fluid.The dry wet ratio of lung tissue was detected.The reagent kit was applied to detect MDA content,SOD and CAT activities in lung tissue.HE staining was applied to observe the pathological morphology of rat lung tissue.Western blotting was applied to detect the expression of IRE1α,TXNIP,NLRP3,Caspase-1,and Cleaved Caspase-3 proteins in lung tissue.Results:Compared with the CK group,the lung tissue morphology in the Model group was obviously damaged,the levels of PEF,FVC,and FEV0.3/FVC,PaO_(2),OI,level of IL-10 in alveolar lavage fluid,and activities of CAT and SOD in lung tissue reduced,the level of PaCO_(2),levels of IL-1β,IL-6,TNF-αin bronchoalveolar lavage fluid,pathological score of lung tissue,content of MDA in lung tissue,and protein expression levels of IRE1α,TXNIP,NLRP3,Caspase-1,and Cleaved Caspase-3 increased(P<0.05).Compared with the Model group,the lung tissue damage in rats in the leonurine-L and leonurine-H groups was obviously reduced,the levels of PEF,FVC,and FEV0.3/FVC,PaO_(2),OI,level of IL-10 in alveolar lavage fluid,and activities of CAT and SOD in lung tissue increased,the level of PaCO_(2),levels of IL-1β,IL-6,TNF-αin bronchoalveolar lavage fluid,pathological score of lung tissue,content of MDA in lung tissue,and protein expression levels of IRE1α,TXNIP,NLRP3,Caspase-1,and Cleaved Caspase-3 decreased(P<0.05).HY-N2485 was able to weaken the improvement effect of leonurine on ARDS rats(P<0.05).Concl

关 键 词：急性呼吸窘迫综合征 炎症 益母草碱 IRE1α/TXNIP/NLRP3信号通路 大鼠 

分 类 号：R285.5[医药卫生—中药学]