基于TGF-β1/Smad、NF-κB的中药干预哮喘气道重塑实验研究进展  

Experimental Research Progress of TGF-β1/Smad,NF-κB-based Herbal Medicine Intervention for Asthma Airway Remodeling

作　　者：黄文鑫 石绍顺[2] HUANG Wenxin;SHI Shaoshun(Liaoning University of Traditional Chinese Medicine,Shenyang 110847,Liaoning,China;The Second Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110034,Liaoning,China)

机构地区：[1]辽宁中医药大学,辽宁沈阳110847 [2]辽宁中医药大学附属第二医院,辽宁沈阳110034

出　　处：《辽宁中医药大学学报》2023年第9期127-133,共7页Journal of Liaoning University of Traditional Chinese Medicine

基　　金：辽宁省自然科学基金指导计划项目(20180550561);国家中医药管理局第五批全国中医临床优秀人才研修项目(国中医药办人教函[2021]271号)。

摘　　要：气道重塑是支气管哮喘发展过程中的关键病理变化,是其反复发作、迁延难愈的重要因素之一。近年来,中医药界围绕哮喘气道重塑相关信号通路开展了大量实验探索,该文综述了近5年来中药调控转化生长因子-β1(TGF-β1)/信号转导蛋白(Smad)、核因子κB(NF-κB)等通路干预哮喘气道重塑的作用和机制。研究表明,中医主要以清热化痰平喘,降气化痰平喘,温阳化痰平喘,寒热同调、补泻兼施,健脾化痰平喘,润肺补虚化痰平喘,益气固本,解表宣肺平喘,温阳平喘等治法调控信号通路。中药单体抑制气道重塑主要选择化痰平喘、活血化瘀功效的中药。中药调控TGF-β1/Smad主要通过下调TGF-β1、Smad2、Smad3、Smad4的表达,或提高Smad6、Smad7的表达,减轻气道上皮纤维化,抑制胶原纤维沉着,抑制气道上皮间充质转化,达到改善气道重塑的目的。中药调控NF-κB一方面通过抑制Toll样受体4(TLR4)通路的活性,下调TLR4、肿瘤坏死因子受体相关因子6(TRAF6)、髓样细胞分化蛋白88(MyD88)、白细胞介素-4(IL-4)、白细胞介素-5(IL-5)、白细胞介素-13(IL-13)、p38丝裂原活化蛋白激酶(p38MAPK)、NF-κB p65 mRNA表达;另一方面升高NF-κB抑制因子α(IκBα)的蛋白表达水平,抑制气道平滑肌增殖,减弱气道高反应性和细胞因子的产生而改善哮喘气道重塑。Airway remodeling is a key pathological change in the development of bronchial asthma,which is one of the important factors for its recurrent attacks and persistent treatment.In recent years,the TCM community has conducted a lot of experimental exploration around the signaling pathways related to asthma airway remodeling.This paper reviews the role and mechanism of TCM in modulating transforming growth factor-β1(TGF-β1)/signal transducer protein(Smad),nuclear factor κB(NF-κB)and other pathways to intervene in asthma airway remodeling in the past five years.Studies have shown that TCM mainly regulates the signaling pathways by clearing heat and resolving phlegm to calm asthma;lowering Qi and resolving phlegm to calm asthma;warming Yang and resolving phlegm to calm asthma;regulating both cold and heat,tonifying and dipping;strengthening the spleen and resolving phlegm to calm asthma;moistening the lung and replenishing deficiency to resolve phlegm and calm asthma;benefiting Qi and consolidating the root;relieving the surface of the lung to calm asthma;and warming Yang to calm asthma.The selection of Chinese herbal monomers to inhibit airway remodeling was mainly derived from Chinese herbal medicines with the efficacy of resolving phlegm and asthma,activating blood circulation and resolving blood stasis.TGF-β1/Smad modulation by Chinese herbal medicine mainly through down-regulating the expression of TGF-β1,Smad2,Smad3,Smad4,or increasing the expression of Smad6,Smad7,reducing airway epithelial fibrosis,inhibiting collagen fiber deposition,and inhibiting airway epithelial mesenchymal transition,to improve airway remodeling.Chinese medicine modulates NF-κB by inhibiting the activity of Toll-like receptor 4(TLR4)pathway to downregulate the expression of TLR4,tumor necrosis factor receptor-associated factor 6(TRAF6),myeloid differentiation protein 88(MyD88),interleukin-4(IL-4),interleukin-5(IL-5),interleukin-13(IL-13),p38 MAPK and NF-κB p65 mRNA;On the other hand,the protein expression level of NF-κB inhibitor

关 键 词：哮喘 气道重塑 信号通路 中药 研究进展 

分 类 号：R256.12[医药卫生—中医内科学] R562.25[医药卫生—中医学]