基于“气道神经源性炎症-TRP通路”探讨慢性咳嗽发病机制及中医治疗
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摘要
咳嗽临床常见,尤其是胸部影像学无明显异常的慢性咳嗽,病因复杂、易误诊误治,逐渐受到重视,国内外相继颁发相关指南,目前认为咳嗽高敏感性是其重要的病理生理机制。中医将慢性咳嗽归于"久咳""久嗽"范畴,在病因病机、治法方药上积累了丰富的临床经验,史利卿教授团队针对该病开展了专项临床及基础研究15年,根据传统中医理论及其突出临床症状提出"风邪伏肺"病机,应用祛风宣肺法治疗效果显著。文章结合西医学相关咳嗽机制研究进展及既往研究结果,初步探讨祛风宣肺法治疗该病的疗效机制,丰富慢性咳嗽风邪伏肺致咳相关学术理论的科学内涵,有利于提高中医药防治慢性咳嗽学术水平。
Cough is common in clinic,especially for chronic cough with no obvious abnormality in chest imaging. The cause of cough is complex and it is easy to be misdiagnosed and mistreated. More attention has been paid to it,and relevant domestic and abroad guidelines have been issued. At present,cough hypersensitivity is considered as an important pathophysiological mechanism.In traditional chinese medicine,chronic cough is due to "long-term cough" category,have accumulated rich clinical experience on the etiology,pathogenesis,therapy and formulas,the author's team have focused on the disease and have done special clinical and basic researches for 15 years,according to the theory of traditional Chinese medicine and its prominent clinical symptoms put forward that "the wind evil fu lung"pathogenesis,the effect of expelling wind and releasing lung is remarkable. In this paper,combined with modern research progress of cough mechanism and previous study results,aim to discuss preliminarily the curative effect mechanism of expelling wind and releasing lung in the treatment of the disease,to enrich the scientific connotation of academic theories that wind evil fu lung pathogenesis in chronic cough,to improve the academic level of traditional Chinese medicine prevention and treatment of chronic cough.
Cough is common in clinic,especially for chronic cough with no obvious abnormality in chest imaging. The cause of cough is complex and it is easy to be misdiagnosed and mistreated. More attention has been paid to it,and relevant domestic and abroad guidelines have been issued. At present,cough hypersensitivity is considered as an important pathophysiological mechanism.In traditional chinese medicine,chronic cough is due to "long-term cough" category,have accumulated rich clinical experience on the etiology,pathogenesis,therapy and formulas,the author's team have focused on the disease and have done special clinical and basic researches for 15 years,according to the theory of traditional Chinese medicine and its prominent clinical symptoms put forward that "the wind evil fu lung"pathogenesis,the effect of expelling wind and releasing lung is remarkable. In this paper,combined with modern research progress of cough mechanism and previous study results,aim to discuss preliminarily the curative effect mechanism of expelling wind and releasing lung in the treatment of the disease,to enrich the scientific connotation of academic theories that wind evil fu lung pathogenesis in chronic cough,to improve the academic level of traditional Chinese medicine prevention and treatment of chronic cough.
引文
[1] Morice AH,Fontana GA,Belvisi MG,et al. ERS guidelines on the assessment of cough[J]. Eur Respir J,2007,29(6):1256-1276.
[2] A.H. Morice and committee members. The diagnosis and management of chronic cough[J]. Eur Respir J,2004,24:481-492.
[3] Irwin RS,French CT,Lewis SZ,et al. Overview of the management of cough:CHEST Guideline and Expert Panel Report[J]. Chest,2014,146(4):885-889.
[4] Irwin RS,French CL,Chang AB,et al. Classification of Cough as a Symptom in Adults and Management Algorithms:CHEST Guideline and Expert Panel Report[J]. Chest,2018,153(1):196-209.
[5] Chin KR,Ji YJ,Sei WL,et al. The Korean Cough Guideline:Recommendation and Summary Statement[J].Tuberc Respir Dis,2016,79(1):14-21.
[6]中华医学会呼吸病学分会哮喘学组.咳嗽的诊断与治疗指南(2015)[J].中华结核和呼吸杂志,2016,39(5):323-354.
[7]赖克方,钟南山.慢性咳嗽[M].北京:人民卫生出版社,2008.
[8] Barnes PJ.Pathophysiology of asthma[J]. Eur Respir Mon,2003,23:84-113.
[9] Muraki M,Iwanaga T,Haraguchi R,et al.Continued inhalation of lidocaine suppresses antigen-induced airway hyperreactivity and airway inflammation in ovalbumin-sensitized guinea pigs[J].Int Immuno-pharmacol,2008,8(5):725-731.
[10] Luo YL,Li PB,Zhang CC,et al.Effects of four antitussives on airway neurogenic inflammation in a guinea pig model of chronic cough induced by cigarette smoke exposure[J].Inflamm Res,2013,62(12):1053-61.
[11] Barnes PJ.Neurogenic inflammation in the airways[J]. Resp Physiol,2001,125(1-2):145-154.
[12] Grace MS,Baxter M,Belvisi MG,et al. Transient receptor potential(TRP)channels in the airway:role in airway disease. Br J Pharmacol,2014,171(10):2593-607.
[13] Grace MS,Dubuis E,Belvisi MG,et al.Pre-clinical studies in cough research:role of Transient Receptor Potential(TRP)channels[J].Pulm Pharmacol Ther,2013,26(5):498-507.
[14] De Logu F,Patacchini R,Fontana G,et al.TRP functions in the broncho-pulmonary system[J]. Semin Immunopathol,2016,38(3):321-329.
[15] Bonvini SJ,Birrell MA,Belvisi MG.Targeting TRP channels for chronic cough:from bench to bedside[J].Naunyn Schmiedebergs Arch Pharmacol,2015,388(4):401-20.
[16] Wallace H. Airway Pathogenesis Is Linked to TRP Channels. In:Emir TLR,editor. Neurobiology of TRP Channels. 2nd edition. Boca Raton(FL):CRC Press/Taylor&Francis,2017:Chapter 13.
[17] Bonvini SJ,Belvisi MG.Cough and airway disease:The role of ion channels[J]. Pulm Pharmacol Ther,2017,47:21-28.
[18] Lee LY,Hsu CC,Lin YJ,et al. Interaction between TRPA1 and TRPV1:Synergy on pulmonary sensory nerves[J]. Pulm Pharmacol Ther,2015,35:87-93.
[19] Yang H,Li S. Transient Receptor Potential Ankyrin 1(TRPA1)Channel and Neurogenic Inflammation in Pathogenesis of Asthma[J].Med Sci Monit,2016,22:2917-2923.
[20] Indranil M,Abhay K,Sarika A,et al. Transient receptor potential ankyrin 1 receptor activation in vitro and in vivo by pro-tussive agents:GRC17536 as a promising anti-tussive therapeutic[J]. PLoS One,2014,9(5):e97005.
[21] Park J J,Lee J,Kimm A,et al.Induction of total insensitivity to capsaicin and hypersensitivity to garlic extract in human by decreased expression of TRPVl[J]. Neurosci Lett,2007,411(2):87-91.
[22] El-Hashim AZ,Jaffal SM,Al-Rashidi FT,et al.Nerve growth facaor enhances cough via a central mechanism of acaion[J].Pharmaco Res,2013,74:68-77.
[23]史利卿,马建岭.风咳的证因浅探[J].环球中医药,2009,2(3):49-51.
[24]史利卿,林彬,马建岭,等.感染后咳嗽的中医证因特点初探[J].中华中医药杂志,2016,31(2):595-597.
[25]史锁芳.慢性咳嗽的证治思路概要[J].江苏中医药,2008,40(7):11-12.
[26]晁恩祥.“风咳”证治探要.江苏中医药,2008,40(7):12-13.
[27]温绍惠,席宁,史利卿. 72例慢性咳嗽患者中医相关病理因素及生活质量调查分析[J].北京中医药大学学报(中医临床版),2011,18(2):17-20.
[28]史利卿,马建岭,杨凯,等.慢性咳嗽中医病因病机及证候学规律的认识与探讨[J].现代中医临床,2017,24(5):1-5.
[29]林彬,史利卿,马建岭,等.慢性咳嗽伏邪病机认识探讨[J].现代中医临床,2017,24(5):12-15.
[30]马建岭,史利卿,席宁.祛风宣肺颗粒治疗感染后咳嗽60例临床观察[J].北京中医药大学学报,2007,30(1):67-69.
[31]王谦,史利卿,马建岭,等.咳嗽敏感性增高豚鼠模型两种造模方法比较研究[J].辽宁中医药大学学报,2017,19(5):92-95.
[32]史利卿,席宁,逯通,等.祛风宣肺方对豚鼠咳嗽模型气道反应性影响的实验研究.北京中医药大学学报,2013,36(10):660-664.
[33]马建岭,温绍惠,席宁,等.祛风宣肺方对气道敏感性增高豚鼠组胺、白三烯B4及嗜中性粒细胞弹力蛋白酶水平的影响[J].中华中医药杂志,2013,28(9):2588-2591.
[34]季坤,马建岭,闫妍,等.祛风宣肺方对豚鼠咳嗽敏感性增高模型的肺组织病理及磷酸化p38丝裂原活化蛋白激酶的影响[J].现代中医临床,2017,24(5):20-24.
[35] Groneberg DA,Niimi A,Dinh QT,etal.Increased expression of transient receptor potential vanilloid-1 in airway nerves of chronic cough[J]. Am J Respir Crit Care Med. 2004 Dec 15;170(12):1276-1280.
[36] Smit LA,Kogevinas M,AntóJM,et al.Transient receptor potential genes,smoking,occupational exposures and cough in adults[J].Respir Res,2012,23,13:26.
[37] Sumner H,Woodcock A,Kolsum U,et al. Predictors of objective cough frequency in chronic obstructive pulmonary disease[J]. Am J Respir Crit Care Med,2013,187(9):943-949.
[2] A.H. Morice and committee members. The diagnosis and management of chronic cough[J]. Eur Respir J,2004,24:481-492.
[3] Irwin RS,French CT,Lewis SZ,et al. Overview of the management of cough:CHEST Guideline and Expert Panel Report[J]. Chest,2014,146(4):885-889.
[4] Irwin RS,French CL,Chang AB,et al. Classification of Cough as a Symptom in Adults and Management Algorithms:CHEST Guideline and Expert Panel Report[J]. Chest,2018,153(1):196-209.
[5] Chin KR,Ji YJ,Sei WL,et al. The Korean Cough Guideline:Recommendation and Summary Statement[J].Tuberc Respir Dis,2016,79(1):14-21.
[6]中华医学会呼吸病学分会哮喘学组.咳嗽的诊断与治疗指南(2015)[J].中华结核和呼吸杂志,2016,39(5):323-354.
[7]赖克方,钟南山.慢性咳嗽[M].北京:人民卫生出版社,2008.
[8] Barnes PJ.Pathophysiology of asthma[J]. Eur Respir Mon,2003,23:84-113.
[9] Muraki M,Iwanaga T,Haraguchi R,et al.Continued inhalation of lidocaine suppresses antigen-induced airway hyperreactivity and airway inflammation in ovalbumin-sensitized guinea pigs[J].Int Immuno-pharmacol,2008,8(5):725-731.
[10] Luo YL,Li PB,Zhang CC,et al.Effects of four antitussives on airway neurogenic inflammation in a guinea pig model of chronic cough induced by cigarette smoke exposure[J].Inflamm Res,2013,62(12):1053-61.
[11] Barnes PJ.Neurogenic inflammation in the airways[J]. Resp Physiol,2001,125(1-2):145-154.
[12] Grace MS,Baxter M,Belvisi MG,et al. Transient receptor potential(TRP)channels in the airway:role in airway disease. Br J Pharmacol,2014,171(10):2593-607.
[13] Grace MS,Dubuis E,Belvisi MG,et al.Pre-clinical studies in cough research:role of Transient Receptor Potential(TRP)channels[J].Pulm Pharmacol Ther,2013,26(5):498-507.
[14] De Logu F,Patacchini R,Fontana G,et al.TRP functions in the broncho-pulmonary system[J]. Semin Immunopathol,2016,38(3):321-329.
[15] Bonvini SJ,Birrell MA,Belvisi MG.Targeting TRP channels for chronic cough:from bench to bedside[J].Naunyn Schmiedebergs Arch Pharmacol,2015,388(4):401-20.
[16] Wallace H. Airway Pathogenesis Is Linked to TRP Channels. In:Emir TLR,editor. Neurobiology of TRP Channels. 2nd edition. Boca Raton(FL):CRC Press/Taylor&Francis,2017:Chapter 13.
[17] Bonvini SJ,Belvisi MG.Cough and airway disease:The role of ion channels[J]. Pulm Pharmacol Ther,2017,47:21-28.
[18] Lee LY,Hsu CC,Lin YJ,et al. Interaction between TRPA1 and TRPV1:Synergy on pulmonary sensory nerves[J]. Pulm Pharmacol Ther,2015,35:87-93.
[19] Yang H,Li S. Transient Receptor Potential Ankyrin 1(TRPA1)Channel and Neurogenic Inflammation in Pathogenesis of Asthma[J].Med Sci Monit,2016,22:2917-2923.
[20] Indranil M,Abhay K,Sarika A,et al. Transient receptor potential ankyrin 1 receptor activation in vitro and in vivo by pro-tussive agents:GRC17536 as a promising anti-tussive therapeutic[J]. PLoS One,2014,9(5):e97005.
[21] Park J J,Lee J,Kimm A,et al.Induction of total insensitivity to capsaicin and hypersensitivity to garlic extract in human by decreased expression of TRPVl[J]. Neurosci Lett,2007,411(2):87-91.
[22] El-Hashim AZ,Jaffal SM,Al-Rashidi FT,et al.Nerve growth facaor enhances cough via a central mechanism of acaion[J].Pharmaco Res,2013,74:68-77.
[23]史利卿,马建岭.风咳的证因浅探[J].环球中医药,2009,2(3):49-51.
[24]史利卿,林彬,马建岭,等.感染后咳嗽的中医证因特点初探[J].中华中医药杂志,2016,31(2):595-597.
[25]史锁芳.慢性咳嗽的证治思路概要[J].江苏中医药,2008,40(7):11-12.
[26]晁恩祥.“风咳”证治探要.江苏中医药,2008,40(7):12-13.
[27]温绍惠,席宁,史利卿. 72例慢性咳嗽患者中医相关病理因素及生活质量调查分析[J].北京中医药大学学报(中医临床版),2011,18(2):17-20.
[28]史利卿,马建岭,杨凯,等.慢性咳嗽中医病因病机及证候学规律的认识与探讨[J].现代中医临床,2017,24(5):1-5.
[29]林彬,史利卿,马建岭,等.慢性咳嗽伏邪病机认识探讨[J].现代中医临床,2017,24(5):12-15.
[30]马建岭,史利卿,席宁.祛风宣肺颗粒治疗感染后咳嗽60例临床观察[J].北京中医药大学学报,2007,30(1):67-69.
[31]王谦,史利卿,马建岭,等.咳嗽敏感性增高豚鼠模型两种造模方法比较研究[J].辽宁中医药大学学报,2017,19(5):92-95.
[32]史利卿,席宁,逯通,等.祛风宣肺方对豚鼠咳嗽模型气道反应性影响的实验研究.北京中医药大学学报,2013,36(10):660-664.
[33]马建岭,温绍惠,席宁,等.祛风宣肺方对气道敏感性增高豚鼠组胺、白三烯B4及嗜中性粒细胞弹力蛋白酶水平的影响[J].中华中医药杂志,2013,28(9):2588-2591.
[34]季坤,马建岭,闫妍,等.祛风宣肺方对豚鼠咳嗽敏感性增高模型的肺组织病理及磷酸化p38丝裂原活化蛋白激酶的影响[J].现代中医临床,2017,24(5):20-24.
[35] Groneberg DA,Niimi A,Dinh QT,etal.Increased expression of transient receptor potential vanilloid-1 in airway nerves of chronic cough[J]. Am J Respir Crit Care Med. 2004 Dec 15;170(12):1276-1280.
[36] Smit LA,Kogevinas M,AntóJM,et al.Transient receptor potential genes,smoking,occupational exposures and cough in adults[J].Respir Res,2012,23,13:26.
[37] Sumner H,Woodcock A,Kolsum U,et al. Predictors of objective cough frequency in chronic obstructive pulmonary disease[J]. Am J Respir Crit Care Med,2013,187(9):943-949.