2022年医学专题—炎症反应双通道幻灯片.ppt

Slide 1,哮喘症状(zhngzhung)由尚未被控制的气道炎症所致炎症反应的双通道,第一页，共二十八页。,Slide 2,Adapted from National Institutes of Health Global Initiative for Asthma:Global Strategy for Asthma Management and Prevention:A Pocket Guide for Physicians and Nurses.Publication No.95-3659B.Bethesda,MD:National Institutes of Health,1998;Bjermer L Respir Med 2001;95:703-719.,炎症(ynzhng)反应在哮喘中的重要性,哮喘本质上是一种炎症反应疾病炎症反应导致气管收缩及气道高反应性，从而产生症状对轻中度哮喘病人应首先(shuxin)进行控制炎症的治疗,第二页，共二十八页。,Slide 3,抑制(yzh)多种炎症介质细胞因子粘附分子可诱导的酶对炎性反应的多种作用,Adapted from Peters-Golden M,Sampson AP J Allergy Clin Immunol 2003;111(suppl 1):S37-S48.,炎症反应(fnyng)的双通道皮质激素的作用,第三页，共二十八页。,Slide 4,尽管(jn gun)使用了吸入激素，气道炎症仍持续存在,ICS=inhaled corticosteroids;OCS ICS=received oral corticosteroids with or without ICSAdapted from Louis R et al Am J Respir Crit Care Med 2000;161:9-16.,20,00010,0001,000100101,Eosinophil 103/gsputum,Controlgroup,轻到中度(zhn d)哮喘,ICSlow-dose(n=10),ICShigh-dose(n=15),OCS(n=10),OCS ICS(n=7),重度哮喘(xiochun),n=74,第四页，共二十八页。,Slide 5,白三烯,其它(qt)炎性介质,This slide is an artistic rendition.Adapted from Holgate ST,Peters-Golden M J Allergy Clin Immunol 2003;111(1 suppl):S1-S4;Holgate ST et al J Allergy Clin Immunol 2003;111(1 suppl):S18-S36;Henderson WR Jr et al Am J Respir Crit Care Med 2002;165:108-116;Peters-Golden M,Sampson AP J Allergy Clin Immunol 2003;111(1 suppl):S37-S42;Varner AE,Lemanske RF Jr.In Asthma and Rhinitis.Oxford,UK:Blackwell Science,2000:1172-1185.,无炎症(ynzhng)反应,炎症(ynzhng)反应,哮喘,白三烯：在哮喘早期及疾病全程中的重要性,第五页，共二十八页。,Slide 6,炎症反应(fnyng)的双通道 半胱氨酰白三烯受体的表达,Neutrophil,Monocyte,Macrophage,Basophil,Pluripotent hemopoieticstem cell,T Cells,Eosinophil,B Lymphocyte,CCR3,CD4+,CD8+,CD19,M-CSF,GM-CSF,IL-3,LTC4,LTD4,LTE4,LN5,Mast Cell,LTC4,LTD4,LTE4,M-CSF,GM-CSF,IL-5,IL-3,GM-CSF,LTC4,LTD4,LTE4,CD14,IL5R,Adapted from Figueroa DJ et al Am J Respir Crit Care Med 2001;163:226-233;Mellor et al Proc Natl Acad Sci USA 2001;98:7964-7969,CysLT1R,CD34+,第六页，共二十八页。,Slide 7,炎症(ynzhng)反应的双通道 半胱氨酰白三烯在炎性细胞受体上的作用,嗜酸细胞(xbo),肺巨噬细胞,Smooth-musclecell,B淋巴细胞,CysLT=cysteinyl leukotriene;PBMC=peripheral blood mononuclear cellsAdapted from Figueroa DJ et al Am J Respir Crit Care Med 2001;163:226-233.,单核细胞,第七页，共二十八页。,Slide 8,Adapted from Peters-Golden M,Sampson AP J Allergy Clin Immunol 2003;111(suppl 1):S37-S48.,炎症(ynzhng)反应的双通道白三烯是强大的炎症介质,其它(qt)介质受体,其它(qt)介质,光胱氨酰白三烯受体,光胱氨酰白三烯,第八页，共二十八页。,Slide 9,Adapted from Hay DWP et al Trends Pharmacol Sci 1995;16:304-309.,炎症(ynzhng)细胞(肥大细胞,嗜酸性细胞),感觉神经(n ju shn jn)(C纤维),CysLTs,水肿(shuzhng),血管,粘液转运减少,嗜酸性细胞内流,阳离子蛋白释放，上皮细胞损伤,收缩和增生,粘液分泌增多,气道上皮,炎症反应的双通道半胱氨酰白三烯在哮喘中的核心作用,第九页，共二十八页。,Slide 10,p=NS between groupsAdapted from OShaughnessy KM et al Am Rev Respir Dis 1993;147:1472-1476.,18.7,201612840,Urinary LTE4excretion(ng/mmolcreatinine),18.4,Placebo,Fluticasone propionate,吸入丙酸氟替卡松对尿中白三烯量的影响(yngxing),1000g,虽然(surn)氟替卡松明显改善了过敏原诱导的支气管狭窄(p 0.02),但在降低尿LTE4浓度方面无显著效果,治疗(zhlio)期14天,洗脱期21天后交叉，最后一天过敏原刺激,N=10,第十页，共二十八页。,Slide 11,*,*p0.05 vs.baselineAdapted from Dworski R et al Am J Respir Crit Care Med 1994;149:953-959.,0.30.20.10,Urinary LTE4(ng/mgcreatinine),Post-allergen challenge,Baseline,ControlPrednisone,*,口服(kuf)强的松对尿中白三烯量的影响,第十一页，共二十八页。,Slide 12,*p0.02 vs.normal individuals;*p0.05 vs.normal individualsAdapted from Pavord ID et al Am J Respir Crit Care Med 1999;160:1905-1909.,14121086420,SputumCysLT levels(ng/ml),Controls控制(kngzh)(n=10),6.4,All patients with asthma所有哮喘(xiochun)患者(n=26),9.4*,Patients with persistent asthma持续性哮喘(xiochun)(n=10),11.4*,Patients with acute attacks急性发作(n=12),13*,吸入糖皮质激素对痰中白三烯水平的影响,第十二页，共二十八页。,Slide 13,LABA=long-acting beta2 agonistAdapted from Currie GP et al Am J Respir Crit Care Med(in press).,0100200,Change ineosinophils(106/L)from run-in,ICS+LABA+Montelukast,ICS+LABA,ICS,ICS+Montelukast,p0.05,p0.05,而白三烯受体拮抗剂孟鲁司特在ICS基础(jch)上可进一步减少气道炎症,炎症反应的双通道长效2受体激动剂不具有(jyu)抗炎作用,第十三页，共二十八页。,Slide 14,*p0.05 compared with beclomethasoneAdapted from LaViolette M et al Am J Respir Crit Care Med 1999;160:1862-1868.,0.120.100.080.060.040.020,Eosinophilcounts(changefrom baseline 103/l),Placebo,Beclomethasone,Montelukast+beclomethasone,Montelukast,*,1*,Treatment group,同时针对炎症双通道的治疗可更好控制(kngzh)哮喘炎症,炎症(ynzhng)反应的双通道白三烯受体拮抗剂孟鲁司特可进一步减少气道炎症,第十四页，共二十八页。,Slide 15,block steroid-sensitivemediators,blocks the effects of CysLTs,吸入激素(j s),孟鲁司特,白三烯受体拮抗剂与皮质激素联合，作用(zuyng)于炎症反应的双通道,The slide represents an artistic rendition.Adapted from Peters-Golden M,Sampson AP J Allergy Clin Immunol 2003;111(1 suppl):S37-S42;Bisgaard H Allergy 2001;56(suppl 66):7-11.,对类固醇敏感(mngn)的介质play a key role in asthmatic inflammation,光胱氨酰白三烯play a key role in asthmatic inflammation,类固醇不能抑制有症状的哮喘病人气道中的半胱氨酰白三烯的形成,双通道,第十五页，共二十八页。,Slide 16,抑制多种用炎症介质(TNF、IL-6、粘附分子）抑制炎症反应(fnyng)过程通过白三烯通道通过对激素敏感的通道,LTRAs=leukotriene receptor antagonistsAdapted from Peters-Golden M,Sampson AP J Allergy Clin Immunol 2003;111(suppl 1):S37-S48.,炎症反应(fnyng)的双通道白三烯受体拮抗剂的作用,第十六页，共二十八页。,Slide 17,第十七页，共二十八页。,18,阿司匹林(s p ln)哮喘的发病机制,花生(hu shn)四烯酸 环氧化酶 脂氧化酶（COX）（5-LO）前列腺素 白 三 烯（LTC4合成酶）,第十八页，共二十八页。,19,阿司匹林哮喘(xiochun)的治疗与管理,避免使用阿司匹林和非类固醇类抗炎药（NSAIDs）脱敏治疗(zhlio)白三烯受体拮抗剂及