Article(id=1322922792668234515, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1322922680609014711, articleNumber=null, orderNo=null, doi=10.13193/j.issn.1673-7717.2025.02.028, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=null, receivedDateStr=null, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1793338972489, onlineDateStr=2026-10-30, pubDate=1739116800000, pubDateStr=2025-02-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1793338972489, onlineIssueDateStr=2026-10-30, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1793338972489, creator=13701087609, updateTime=1793338972489, updator=13701087609, issue=Issue{id=1322922680609014711, tenantId=1146029695717560320, journalId=1255847919539208197, year='2025', volume='43', issue='2', pageStart='1', pageEnd='258', issueExtLink='null', onlineDate='null', pubDate='1739116800000', pubDateStr='2025-02-10', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1793338945772, creator='13701087609', updateTime=1793340618065, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1322929694785536732, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1322922680609014711, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1322929694785536733, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1322922680609014711, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=122, endPage=126, ext={EN=ArticleExt(id=1322922792873755412, articleId=1322922792668234515, tenantId=1146029695717560320, journalId=1255847919539208197, language=EN, title=Role of NLRP3 Inflammasome in Pathogenesis of Asthma and Research Progress on Traditional Chinese Medicine Intervention, columnId=1256183361521967297, journalTitle=Chinese Archives of Traditional Chinese Medicine, columnName=Target on National Project, runingTitle=null, highlight=null, articleAbstract=

Asthma,characterized as an inflammatory disease of the airways,arises from a myriad of intricate causes. Existing studies have shown that the formation of asthma are heavily influenced by the NLRP3 inflammasome and other cellular inflammatory factors. Traditional Chinese medicine(TCM)has a significant therapeutic effect on asthma,but the mechanism is not known. This article aims to provide a review of TCM therapies such as TCM compound formulations that regulate the NLRP3 inflammasome and related cellular inflammatory factor system in the treatment of asthma. Studies have found that traditional Chinese medicine can positively influence asthma by modulating the immune system,enhancing the body's ability to remove reactive oxygen species(ROS)and improving endoplasmic reticulum stress levels,providing reference for further exploring the scientific effectiveness of TCM targeting NLRP3 inflammasome in the treatment of asthma.

, authors=Jiahan LIU1, Xingxing YUAN1, 2, Bingyou YANG1, authorsList=Jiahan LIU, Xingxing YUAN, Bingyou YANG, authorCompany=null, correspAuthors=Bingyou YANG, authorNote=null, correspAuthorsNote=null, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, fund=null), CN=ArticleExt(id=1322922793897165595, articleId=1322922792668234515, tenantId=1146029695717560320, journalId=1255847919539208197, language=CN, title=NLRP3炎症小体在哮喘发病机制中的作用及中医药干预研究进展, columnId=1256183362172142382, journalTitle=中华中医药学刊, columnName=国家项目点击, runingTitle=null, highlight=null, articleAbstract=

哮喘属于一种气道炎性疾病,其产生原因非常复杂。现有研究表明,NLRP3炎症小体及相关细胞炎症因子在哮喘的形成和发展中扮演关键角色。中医药治疗哮喘疗效显著,但具体机制尚不明确。对调控NLRP3炎症小体及相关细胞炎症因子系统治疗哮喘的中药复方制剂、中药单味药及其有效成分及中医外治等中医药疗法进行综述,发现中医药可以通过调节免疫系统、提高活性氧清除能力和改善内质网应激水平等途径干预哮喘。为进一步探索中医药靶向NLRP3炎症小体治疗哮喘的科学有效性提供参考。

, authors=刘珈含1, 袁星星1, 2, 杨炳友1, authorsList=刘珈含, 袁星星, 杨炳友, authorCompany=null, correspAuthors=杨炳友, authorNote=

刘珈含(1986-),女,黑龙江哈尔滨人,博士在读,研究方向:北药药效物质基础。

, correspAuthorsNote=
杨炳友(1970-),男,黑龙江饶河人,教授,博士研究生导师,博士,研究方向:北药药效物质基础。E-mail:。
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刘珈含(1986-),女,黑龙江哈尔滨人,博士在读,研究方向:北药药效物质基础。

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刘珈含(1986-),女,黑龙江哈尔滨人,博士在读,研究方向:北药药效物质基础。

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OxLDL-induced IL-1 beta secretion promoting foam cells formation was mainly via CD36 mediated ROS production leading to NLRP3 inflammasome activation[J]. Inflamm Res,2014,63(1):33-43., articleTitle=OxLDL-induced IL-1 beta secretion promoting foam cells formation was mainly via CD36 mediated ROS production leading to NLRP3 inflammasome activation, refAbstract=null), Reference(id=1322922805133706100, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322922792668234515, doi=null, pmid=null, pmcid=null, year=2022, volume=283, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[45], rfOrder=44, authorNames=XU L T, WANG T, FANGK L, journalName=J Ethnopharmacol, refType=null, unstructuredReference=XU L T,WANG T,FANGK L,et al. The ethanol extract of flower buds of Tussilago farfara L. attenuates cigarette smoke-induced lung inflammation through regulating NLRP3 inflammasome,Nrf2,and NF-κB[J]. 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The complex interplay between endoplasmic reticulum stress and the NLRP3 inflammasome:a potential therapeutic target for inflammatory disorders[J]. 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种类代表药物作用相关指标文献
中药复方制剂玉屏风散减轻肺组织中炎症细胞浸润和黏液分泌NLRP3、TNF-α、IL-6、IL-1 β、ASC、Caspase-1↓[25]
苏黄止咳胶囊抑制炎症细胞,改善哮喘症状NLRP3、Caspase-1、IL-1 β↓[26]
小青龙汤下调炎症细胞、减轻气道炎症NLRP3、IL-1、NF-κB↓[27]
单味中药及其活性成分清肺口服液缓解气道炎症和气道高反应性NLRP3、Caspase-1、IL-1 β↓[28]
穿心莲内酯降低支气管肺泡液和血清中细胞因子蛋白水平TNF-α、NF-κB、NLRP3、IL-1 β↓[29]
白藜芦醇减轻炎症细胞浸润及肺水肿NLRP3、ASC、Caspase-1、IL-1 β、IL-18↓[30]
中医外治法苦杏仁苷抑制炎症细胞浸润,缓解肺损伤TNF-α、NF-κB、NLRP3、IL-6、IL-1 β↓[31]
川贝母减轻肺组织病理损伤NLRP3、IL-1、IL-18↓[32]
针灸显著抑制小鼠气道周围炎性细胞、黏液分泌IgE、CCL5、CCL11、IL-17A、IL-4、IL-5、IL-13↓[33]
艾灸改善肺泡壁结构、维护细支气管形态、促进呼吸道通畅性以及保护上皮细胞IgE、IL-1 β↓[34]
中药穴位贴敷抑制炎症细胞因子,改善过敏症状IgE、IL-4↓、Th1/Th2↑[35]
), ArticleFig(id=1322922798137606979, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322922792668234515, language=CN, label=表1, caption=

中医药对NLRP3炎症小体及相关细胞炎症因子的调控作用

, figureFileSmall=null, figureFileBig=null, tableContent=
种类代表药物作用相关指标文献
中药复方制剂玉屏风散减轻肺组织中炎症细胞浸润和黏液分泌NLRP3、TNF-α、IL-6、IL-1 β、ASC、Caspase-1↓[25]
苏黄止咳胶囊抑制炎症细胞,改善哮喘症状NLRP3、Caspase-1、IL-1 β↓[26]
小青龙汤下调炎症细胞、减轻气道炎症NLRP3、IL-1、NF-κB↓[27]
单味中药及其活性成分清肺口服液缓解气道炎症和气道高反应性NLRP3、Caspase-1、IL-1 β↓[28]
穿心莲内酯降低支气管肺泡液和血清中细胞因子蛋白水平TNF-α、NF-κB、NLRP3、IL-1 β↓[29]
白藜芦醇减轻炎症细胞浸润及肺水肿NLRP3、ASC、Caspase-1、IL-1 β、IL-18↓[30]
中医外治法苦杏仁苷抑制炎症细胞浸润,缓解肺损伤TNF-α、NF-κB、NLRP3、IL-6、IL-1 β↓[31]
川贝母减轻肺组织病理损伤NLRP3、IL-1、IL-18↓[32]
针灸显著抑制小鼠气道周围炎性细胞、黏液分泌IgE、CCL5、CCL11、IL-17A、IL-4、IL-5、IL-13↓[33]
艾灸改善肺泡壁结构、维护细支气管形态、促进呼吸道通畅性以及保护上皮细胞IgE、IL-1 β↓[34]
中药穴位贴敷抑制炎症细胞因子,改善过敏症状IgE、IL-4↓、Th1/Th2↑[35]
), ArticleFig(id=1322922798217298756, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322922792668234515, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
种类代表药物机制作用相关指标文献
中药复方制剂祛风宣痹方调节免疫系统改善哮喘小鼠气道炎症细胞浸润等症状IgE、IL-6、IL-18、IL-1β,Th1/Th2↑[40]
中医外治法针灸调节免疫系统改善COPD患者肺功能,改善生活质量及呼吸程度NLRP3↓、Th1/Th2↑[41]
中药复方制剂麻黄定喘汤调节免疫系统减轻气道炎症反应,改善哮喘症状NLRP3、Th17、Caspase-1、IL-18、IL-1β↓[42]
单味中药及其活性成分款冬花提高活性氧(ROS)清除能力减轻肺部炎症NLRP3、NF-κB、ROS↓[45]
单味中药及其活性成分穿心莲内酯提高活性氧(ROS)清除能力减轻肺部炎症程度NLRP3、NF-κB、ROS↓[29]
中药复方制剂苏黄止咳胶囊改善ER应激水平显著缓解肺损伤和功能障碍NLRP3、IL-1、Ca2+、ER↓[26]
单味中药及其活性成分川陈皮素改善ER应激水平减轻哮喘大鼠哮喘气道炎症NLRP3、IL-1β、IL-6、TNF-α、ER↓[46]
), ArticleFig(id=1322922798296990533, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322922792668234515, language=CN, label=表2, caption=

中医药调控NLRP3炎症小体及相关细胞炎症因子的机制

, figureFileSmall=null, figureFileBig=null, tableContent=
种类代表药物机制作用相关指标文献
中药复方制剂祛风宣痹方调节免疫系统改善哮喘小鼠气道炎症细胞浸润等症状IgE、IL-6、IL-18、IL-1β,Th1/Th2↑[40]
中医外治法针灸调节免疫系统改善COPD患者肺功能,改善生活质量及呼吸程度NLRP3↓、Th1/Th2↑[41]
中药复方制剂麻黄定喘汤调节免疫系统减轻气道炎症反应,改善哮喘症状NLRP3、Th17、Caspase-1、IL-18、IL-1β↓[42]
单味中药及其活性成分款冬花提高活性氧(ROS)清除能力减轻肺部炎症NLRP3、NF-κB、ROS↓[45]
单味中药及其活性成分穿心莲内酯提高活性氧(ROS)清除能力减轻肺部炎症程度NLRP3、NF-κB、ROS↓[29]
中药复方制剂苏黄止咳胶囊改善ER应激水平显著缓解肺损伤和功能障碍NLRP3、IL-1、Ca2+、ER↓[26]
单味中药及其活性成分川陈皮素改善ER应激水平减轻哮喘大鼠哮喘气道炎症NLRP3、IL-1β、IL-6、TNF-α、ER↓[46]
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NLRP3炎症小体在哮喘发病机制中的作用及中医药干预研究进展
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刘珈含 1 , 袁星星 1, 2 , 杨炳友 1
中华中医药学刊 | 国家项目点击 2025,43(2): 122-126
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中华中医药学刊 |国家项目点击 2025 , 43 (2) : 122 -126
NLRP3炎症小体在哮喘发病机制中的作用及中医药干预研究进展
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刘珈含1, 袁星星1, 2, 杨炳友1
作者信息
  • 1.黑龙江中医药大学,黑龙江 哈尔滨 150040
  • 2.黑龙江省中医药科学院,黑龙江 哈尔滨 150036
通讯作者:
杨炳友(1970-),男,黑龙江饶河人,教授,博士研究生导师,博士,研究方向:北药药效物质基础。E-mail:。
作者简介:

刘珈含(1986-),女,黑龙江哈尔滨人,博士在读,研究方向:北药药效物质基础。

Role of NLRP3 Inflammasome in Pathogenesis of Asthma and Research Progress on Traditional Chinese Medicine Intervention
Jiahan LIU1, Xingxing YUAN1, 2, Bingyou YANG1
Affiliations
  • 1.Heilongjiang University of Chinese Medicine,Harbin 150040,Heilongjiang,China
  • 2.Heilongjiang Academy of Chinese Medicine Sciences,Harbin 150036,Heilongjiang,China
出版时间: 2025-02-10 doi: 10.13193/j.issn.1673-7717.2025.02.028
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哮喘属于一种气道炎性疾病,其产生原因非常复杂。现有研究表明,NLRP3炎症小体及相关细胞炎症因子在哮喘的形成和发展中扮演关键角色。中医药治疗哮喘疗效显著,但具体机制尚不明确。对调控NLRP3炎症小体及相关细胞炎症因子系统治疗哮喘的中药复方制剂、中药单味药及其有效成分及中医外治等中医药疗法进行综述,发现中医药可以通过调节免疫系统、提高活性氧清除能力和改善内质网应激水平等途径干预哮喘。为进一步探索中医药靶向NLRP3炎症小体治疗哮喘的科学有效性提供参考。

NLRP3  /  炎症小体  /  中医药  /  支气管哮喘  /  气道慢性炎症

Asthma,characterized as an inflammatory disease of the airways,arises from a myriad of intricate causes. Existing studies have shown that the formation of asthma are heavily influenced by the NLRP3 inflammasome and other cellular inflammatory factors. Traditional Chinese medicine(TCM)has a significant therapeutic effect on asthma,but the mechanism is not known. This article aims to provide a review of TCM therapies such as TCM compound formulations that regulate the NLRP3 inflammasome and related cellular inflammatory factor system in the treatment of asthma. Studies have found that traditional Chinese medicine can positively influence asthma by modulating the immune system,enhancing the body's ability to remove reactive oxygen species(ROS)and improving endoplasmic reticulum stress levels,providing reference for further exploring the scientific effectiveness of TCM targeting NLRP3 inflammasome in the treatment of asthma.

NLRP3  /  inflammasome  /  traditional Chinese medicine  /  asthma  /  allergic airway inflammation
刘珈含, 袁星星, 杨炳友. NLRP3炎症小体在哮喘发病机制中的作用及中医药干预研究进展. 中华中医药学刊, 2025 , 43 (2) : 122 -126 . DOI: 10.13193/j.issn.1673-7717.2025.02.028
Jiahan LIU, Xingxing YUAN, Bingyou YANG. Role of NLRP3 Inflammasome in Pathogenesis of Asthma and Research Progress on Traditional Chinese Medicine Intervention[J]. Chinese Archives of Traditional Chinese Medicine, 2025 , 43 (2) : 122 -126 . DOI: 10.13193/j.issn.1673-7717.2025.02.028
核苷酸结合寡聚化结构域样受体(NLR)家族是感觉细胞内病原相关分子模式(PAMPs)和损坏相关分子模式(DAMPs)的胞质蛋白质,其中NLRP3是最广泛研究的成员之一,在多种人类炎症疾病的发生与激活过程中起着重要作用[1]。支气管哮喘属于呼吸系统异质性疾病,常伴有咳嗽、喘息、呼吸困难等反复发作的症状[2]。遗传学研究揭示了人类的NLRP3基因中的两个功能获得单核苷酸多态性(SNPs),它们与过敏性哮喘显著相关[3]。同样,NLRP3的表达水平已被证明在过敏性鼻炎恶化期间在人类鼻上皮细胞中显著上调,在花粉季节在患者中下调[4]。虽然这些发现的功能意义尚不清楚,但有大量证据支持NLRP3炎症小体与哮喘发病密切相关。此外,白术内酯Ⅲ可降低白细胞介素(IL)-4诱导的16HBE细胞和卵清蛋白(OVA)诱导的哮喘小鼠中NLRP3炎症小体的激活,并调节Th1/Th2平衡,提示中医药可能具有治疗哮喘的作用[5]。从这个角度出发,本文讨论了NLRP3结构和分子激活的理解的最新进展,重点介绍了NLRP3炎症小体参与哮喘发病的具体机制及中医药的调控作用。
炎症小体一词最初由Jürg Tschopp及其同事提出,表示细胞内超分子蛋白复合物,其组装后可介导促炎性Caspase-1的激活以及IL-1β的成熟和分泌,以响应病原体和无菌刺激[6]。NLRP3炎症小体结构如插页ⅩⅩⅦ图1所示,因其复合体中的NLRP3蛋白属于NLRs家族而得名[7]。NLRP3炎症小体由传感器蛋白组成,该传感器蛋白在激活后聚集并招募两种额外的蛋白:凋亡相关斑点样蛋白(ASC)和ProCaspase-1。在免疫激活物的存在下,如PAMPs、DAMPs、环境压力或其他外源性刺激物,NLRP3通道的激活引起NLRP3和ASC之间PYD结构域的开放,从而促进了它们之间的相互作用。之后,ASC上的CARD结构域与ProCaspase-1上的CARD结构域结合,形成NLRP3炎症小体[8-9]。为确保适当的免疫活性,这3种蛋白质之间的相互作用严格调控炎症小体的活化。
炎症小体是激活炎症的主要途径之一。研究表明,NLRP3炎症小体可被多种细胞信号激活,激活方式主要由两阶段信号完成,第一阶段信号为多种PAMPs或DAMPs,如病原体感染、细胞损伤、细胞应激等触发的启动信号,第二阶段信号为K+外流、活性氧(ROS)和病毒RNA等刺激引发的激活信号[10-11],如插页ⅩⅩⅦ图2所示。
在炎症小体活化的第一阶段,多种PAMPs或DAMPs通过Toll受体(TLRs)途径可以触发NLRP3炎症小体的启动,这些启动信号会引起一系列的细胞内信号通路反应,最终促使NLRP3蛋白、ASC及ProCaspase-1结合,从而形成起始的NLRP3炎症小体,同时激活ProIL-1β和ProIL-18[12]。分泌的IL-1b和IL-18以环境依赖的方式启动和放大炎症反应[13]。
第二阶段激活信号是NLRP3的寡聚化,活化的NLRP3炎症小体触发了ProCaspase-1向Caspase-1的转化,并刺激IL-1β和IL-18的释放[14]。据报道,有3种途径参与炎症小体第二阶段的激活。第一种途径为离子通道途径。典型代表为ATP介导的K+外流。ATP作为一种NLRP3激动剂,诱导K+通过泛联蛋白-1(Pannexin-1)通道流出,Pannexin-1是一种半通道蛋白,可通过P2X7受体激活打开。这一过程导致了NLRP3炎症小体的激活[15]。此外,PÉTRILLI V等[16]研究表明细胞内和内质网(ER)相关的Ca2+的水平可能影响NLRP3炎症小体的激活。第二种途径为NLRP3激活剂介导的线粒体障碍与ROS途径。典型代表为PAMPs和DAMPs介导的线粒体障碍与ROS升高。PAMPs和DAMPs会引起线粒体内正负电位异常,导致线粒体功能障碍,触发ROS的产生,进而诱导NLRP3炎症小体的组装[17-18]。第三种触发NLRP3炎症小体的途径是环境刺激物引起的溶酶体破裂。当细胞吞噬环境刺激物后形成晶体或颗粒结构,这些聚集物会通过组织蛋白酶B(Cathepsin B)介导的机制使得溶酶体破裂和溶酶体内容物的释放,其中包括一些危险信号分子和诱导炎症的细胞内信号分子。这些溶酶体内容物的释放会进一步激活NLRP3炎症小体,并将进一步启动细胞内的信号传导通路,包括激活IL-1β、IL-18以及诱导细胞凋亡和促发炎细胞因子的释放等[19]。
NLRP3炎症小体是固有免疫系统中一个关键的组分。其激活后可促使细胞分泌炎症因子IL-18和IL-1β到细胞外,从而参与全身炎症反应[19]。有大量研究表明NLRP3炎症小体及下游相关细胞炎症因子在哮喘的气道炎症中发挥着重要作用。血清淀粉样蛋白A通过激活NLRP3炎症小体,从而促进IL-1α、IL-1β、IL-6和IL-23等炎症细胞因子的分泌,从而参与了过敏性哮喘小鼠的病理进展[20]。HIROTA J A等[21]通过检测经城市颗粒物刺激后人气道上皮支气管和原代细胞中的NLRP3炎症小体、IL-1β和IL-18的表达水平,得出了相同的结论。刘力兴等研究发现,在哮喘患者的单个核细胞中,NLRP3 mRNA的表达水平明显增加,同时并观察到IL-18和IL-1β的水平上升。这些结果提示,NLRP3、IL-18和IL-1β在支气管哮喘的气道炎症反应中起到了重要的作用[22]。ZHANG B等[23]发现在抑制了相关细胞炎症因子如IL-1β和肿瘤坏死因子-α(TNF-α)的表达后能显著改善经脂多糖(LPS)诱导的支气管哮喘大鼠模型的肺部损伤和炎症反应。在一项临床回顾性研究中,甲型流感病毒感染的哮喘患者和正常志愿者支气管上皮细胞中炎症小体及下游炎症细胞因子,如Caspase-1、IL-1β等表达增强,这表明炎症小体的激活可能参与了病毒诱导的哮喘的发生发展[24]。以上研究表明NLRP3炎症小体的活化及相关细胞炎症因子的释放共同参与了哮喘气道炎症的发病机制。
中医药被应用于哮喘的治疗已有数千年历史。在哮喘的发病机制中,NLRP3炎症小体和与之相关的炎症因子起着关键的角色。越来越多的研究表明中药复方制剂、单味中药及其活性成分和中医外治均通过调控NLRP3炎症小体,调节相关炎症因子和抑炎因子的表达水平,从而达到缓解哮喘症状、减轻气道炎症及提高患者肺功能的治疗作用,见表1所示。
玉屏风散是一种具有代表性的中药配方,对哮喘具有公认的治疗作用。LIU X等[25]使用LPS刺激的U937细胞和OVA致敏化的BALB/c小鼠模型进行对玉屏风散治疗哮喘的机制进行实验验证。结果表明,玉屏风散显著降低了LPS刺激的U937细胞和哮喘小鼠中TNF-α和IL-6的产生,以及IL-1β、NLRP3、Caspase-1和ASC的mRNA和蛋白质水平。此外,玉屏风散治疗还减轻了哮喘小鼠的临床症状,减少了哮喘小鼠肺组织中炎症细胞浸润和黏液分泌。苏黄止咳胶囊可抑制NLRP3炎症小体的激活,降低裂解的Caspase-1的表达,并减少IL-1β的分泌,从而改善哮喘症状[26]。小青龙汤是临床治疗寒冷性哮喘的首选药物,宋桂华等人的研究表明小青龙汤可显著降低哮喘小鼠血清中IL-1和核因子-κB(NF-κB)水平,这提示小青龙汤可通过下调炎症细胞因子水平,达到减轻气道炎症、缓解哮喘症状的效果[27]。清肺口服液可下调肺组织信号通路中关键蛋白NLRP3、Caspase-1和IL-1β的表达,从而缓解呼吸道合胞病毒感染哮喘小鼠的气道炎症和气道高反应性[28]。NLRP3炎症小体的活化参与了哮喘的发生发展,中药复方制剂可通过调控NLRP3炎症小体的信号通路来缓解哮喘症状。
穿心莲内酯可由植物穿心莲提取而得,其能显著降低经OVA诱导的过敏性哮喘大鼠模型的支气管肺泡液和血清中细胞因子的蛋白水平。此外,穿心莲内酯在体内和体外实验中显著阻碍了NF-κB和NLRP3炎症小体的活化,从而降低了TNF-α和IL-1β的水平[29]。白藜芦醇是一种天然植物抗毒素,其对于哮喘的治疗可能与其抗炎和抗氧化特性有关。LPS哮喘小鼠经白藜芦醇治疗后,小鼠的肺部组织显示出较少的炎症细胞浸润和肺水肿的程度减轻。此外,白藜芦醇逆转了LPS介导的支气管肺泡灌洗液(BALF)中IL-1β和IL-18水平的升高,还抑制肺组织中的NLRP3、ASC、Caspase-1 mRNA和蛋白表达[30]。苦杏仁苷来源于苦杏仁,这是一种有效的中草药。在一项经LPS诱导的哮喘小鼠模型实验中,杏仁苷通过抑制LPS诱导的NF-κB和NLRP3活化,显著降低了LPS诱导的炎症细胞浸润以及BALF中TNF-α、IL-1β和IL-6的产生,从而缓解肺损伤[31]。川贝母作为中医临床常用药材,常作为止咳、平喘的首选药,在临床中已被应用于治疗哮喘。陈艳[32]研究发现预防性使用川贝母,可显著下调LPS哮喘小鼠肺组织中NLRP3、IL-1β和IL-18等炎症趋化因子的mRNA和蛋白表达,从而减轻肺组织病理损伤。以上研究表明,单味中药及其活性成分对于治疗哮喘均具有一定作用,其作用机制可能与抑制NLRP3炎症小体的信号通路有一定关联。
针灸已被长期广泛应用于哮喘的临床治疗,即按照中医理论对哮喘患者的哮喘症状进行分析,并选择相应的穴位进行针刺治疗。唐伟峰等发现,针灸OVA诱导哮喘小鼠的大椎、肺俞等穴位,可显著抑制小鼠气道周围炎性细胞、黏液分泌以及BALF中IgE、趋化因子配体5(CCL5)、CCL11、IL-17A水平和血清中IL-4、IL-5、IL-13水平[33]。
艾灸是一种常见的中医治疗方法,通过点燃艾草产生的热力刺激人体的穴位或特定部位,以达到防病治病的目的。在CHEN X H等[34]的研究中,艾灸经OVA诱导哮喘大鼠的双侧肺俞穴和肾俞穴30 min,1次/d,持续14 d后,OVA大鼠血清中IgE和IL-1β水平明显降低。此外与OVA大鼠相比,艾灸治疗的大鼠能够通过改善肺泡壁结构、维护细支气管形态、促进呼吸道通畅性以及保护上皮细胞等方面的作用,有效地改善肺部状况并缓解哮喘症状。
中药穴位贴敷是一种利用中医经络学原理治疗疾病的非侵入性疗法,它在中医治疗学中占据着极为重要的位置。在一项过敏性哮喘患者的临床研究中,ZHAO S M等对50例过敏性哮喘患者进行了中药穴位贴敷治疗,选用心俞、皮俞、肾俞穴等穴位,治疗后的患者血清中IgE和IL-4水平明显下降,Th1/Th2细胞比率明显升高,过敏性哮喘患者的症状反应明显改善[35-36]。上述研究均表明中医外治法可降低多种细胞炎症因子表达,从而改善哮喘发作症状,但其抑制NLRP3在哮喘中的机制研究尚待完善。
中医药可通过免疫细胞调节、提高抗氧化能力及改善内质网应激水平等多种机制调控NLRP3炎症小体及相关细胞炎症因子,减轻气道高反症状,降低全身炎症反应,从而达到治疗哮喘的作用,见表2、插页ⅩⅩⅧ图3所示。
哮喘是一种呼吸系统异质性疾病,与免疫系统息息相关。人体免疫系统分为适应性免疫(特异性)系统和固有免疫(非特异性)系统。Th1/Th2细胞失衡对适应性免疫系统有着重要影响,同时也是哮喘防治的重要环节。NLRP3炎症小体介导的细胞因子会影响Th2细胞的增殖和IgE抗体的产生[37-38]。BESNARD A G等[39]的研究也证实,IL-1β的缺失导致Th2相关细胞因子的表达降低,包括IL-13、IL-5和IL-33,最终导致过敏性气道炎症的减弱。祛风宣痹方能够降低OVA哮喘小鼠BALF中IgE与促炎细胞因子IL-6、IL-18、IL-1β的分泌水平,恢复Th1/Th2平衡,从而改善哮喘小鼠气道炎症细胞浸润等症状[40]。桂坤[41]基于NLRP3及Th1、Th2平衡角度,对251例慢性阻塞性肺疾病(COPD)患者进行针灸辅助治疗,结果表明针灸可调控NLRP3激活,调节Th1/Th2细胞因子水平,从而改善COPD患者肺功能,改善生活质量及呼吸程度,降低再入院风险。NLRP3是固有免疫系统的重要组成部分,孟庆玲等[42-43]研究表明麻黄定喘汤显著抑制了OVA小鼠的NLRP3炎症小体的活化和Th17细胞相关因子的释放,下调了肺组织中Caspase-1、IL-18、IL-1β等蛋白表达水平。这提示我们中医药干预可调节促炎驱化因子表达、恢复Th1/Th2细胞平衡,降低抗原呈递,抑制T细胞活化,从而减轻气道炎症反应,改善哮喘症状。
研究表明,当线粒体ROS对还原性辅酶Ⅱ等氧化系统造成损害时,将激活NLRP3炎症小体,进而参与气道炎症反应[44]。穿心莲内酯在中国已经使用了数百年,现在它已被正式批准用于治疗呼吸道感染和发烧等。PENG S等的一项研究表明,穿心莲内酯可以抑制OVA诱导的哮喘,其机制可能是提高ROS清除能力后,穿心莲内酯能负向调控NF-κB和NLRP3炎症小体的激活,并减轻小鼠肺部炎症的程度[29]。XU L T等[45]研究表明,款冬花可显著抑制香烟烟雾诱导的肺部炎症小鼠模型中炎症因子如TNF-α和IL-1β的过量产生;在细胞模型中,款冬花不仅能有效降低ROS的产生水平,进而减轻由于ROS过量引发的细胞损伤,还能显著抑制NF-κB和NLRP3炎症小体的活化。这表明款冬花在体内外均能有效减轻肺部炎症。这些结果为中医药在哮喘或炎症性气道疾病中的临床应用提供了证据。
现在人们普遍认为,ER应激和炎症小体在激活炎症信号级联反应中都起着关键作用。苏黄止咳胶囊是一种临床常用的中成药,在长期临床应用中对咳嗽变异性哮喘的治疗和并发症起着至关重要的作用。苏黄止咳胶囊通过调节Ca2+运输改善了ER应激,抑制了NLRP3炎症小体的激活,并减少IL-1β的分泌,从而显著缓解肺损伤和功能障碍[26]。川陈皮素是中国特有的香料和传统药材陈皮的主要成分,具有祛痰平喘、抗炎抗氧化的作用。何邵波等[46]研究表明川陈皮素可以抑制ER应激水平和NLRP3炎症小体激活,减少促炎因子IL-1β、IL-6、TNF-α分泌,从而减轻哮喘大鼠哮喘气道炎症。越来越多的研究结果指出,内质网应激与炎症小体激活导致的炎症级联反应存在密切关系,这可能为一系列炎症疾病的治疗靶向提供了一个新的轴[47]。
在过去的20年里,对NLRP3炎症小体的研究导致了对其功能、信号传导和结构的认识的不断深入,这在很大程度上影响了我们对健康和疾病中炎症的先天免疫传感和调节的理解。认识到异常NLRP3激活和功能对支气管哮喘的炎症状态起着重要的推动作用。支气管哮喘作为一种慢性呼吸系统异质性疾病,发病机制复杂,已经成为当今世界上威胁健康的主要原因。现有研究表明,NLRP3炎症小体被激活并促使其下游的细胞炎症因子的产生。这些细胞炎症因子,如IL-1β和IL-18,能够引发炎症反应并导致气道高反应性和病变。通过干扰NLRP3炎症小体的激活或针对其下游的细胞炎症因子进行靶向治疗,可以有效抑制哮喘的炎症反应,缓解症状并改善疾病预后。中医药干预可通过调节免疫系统、提高ROS清除能力及改善ER应激水平等机制减轻气道炎症、改善哮喘临床症状。除了中药、针灸、艾灸和穴位贴敷等疗法外,中医药还采用推拿等多种方法来治疗哮喘。综上所述,本研究可为发挥传统中医药的优势防治哮喘提供参考,为靶向调控NLRP3炎症小体治疗哮喘提供了药物研发新思路。然而,对于中医外治疗法在治疗哮喘时是否与NLRP3炎症小体的表达存在关联以及具体的机制,仍需要进一步的研究来进行探讨和确认。
  • 国家自然科学基金青年科学基金项目(82205007)
  • 黑龙江省“双一流”学科协同创新成果建设项目(LJGXCG2022-096)
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2025年第43卷第2期
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doi: 10.13193/j.issn.1673-7717.2025.02.028
  • 首发时间:2026-10-30
  • 出版时间:2025-02-10
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国家自然科学基金青年科学基金项目(82205007)
黑龙江省“双一流”学科协同创新成果建设项目(LJGXCG2022-096)
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    1.黑龙江中医药大学,黑龙江 哈尔滨 150040
    2.黑龙江省中医药科学院,黑龙江 哈尔滨 150036

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杨炳友(1970-),男,黑龙江饶河人,教授,博士研究生导师,博士,研究方向:北药药效物质基础。E-mail:。
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鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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