清心培土法对特应性皮炎患者IL-2/TNF-α及其受体的影响和疗效评价
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摘要
自1992年SheeHan等在《柳叶刀》和《英国皮肤病杂志》发表了中医药治疗特应性皮炎可能有效的临床随机对照试验以来,中医药做为一种潜在的有效治疗方法,被越来越多地用于治疗特应性皮炎的临床和实验研究。
     本文从中医药治疗特应性皮炎的文献研究,序贯试验和较长期的随访观察,以及免疫学角度探讨了清心培土法的疗效和作用机理。
     第一部分文献研究
     目的
     探讨特应性皮炎的基本病因和主导病机。分析中医药治疗特应性皮炎的辨旺论治规律。阐述清心培土法治疗特应性皮炎的心脾制衡策略。
     方法
     根据文献分析中医学认识特应性皮炎的历史沿革。根据历代医家的认识,结合特应性皮炎发病特点和临床特征,分析其主导病机和治则治法。全面收集国内外公开发表的中药复方治疗特应性皮炎的文献,运用脏腑辨证结合以方测证的方法分析特应性皮炎中医治疗文献的辨证论治规律。以文献研究结合既往的研究基础阐述清心培土法治疗特应性皮炎的制衡策略。
     结果
     特应性皮炎病因主要归于先天禀赋不耐、胎毒遗热,主导病机关乎心火,脾虚,心火耗伤元气,脾虚导致心火,心火脾虚交织互见,虚实错杂。
     辨证复方治疗特应性皮炎侧重于运用心经药物,辨病复方治疗特应性皮炎侧重于运用肝经药物,日本汉方治疗特应性皮炎侧重于运用肺经药物;三者均将脾经作为最重要的药物治疗靶点。心脾、肝脾、肝肾、脾肺经用药存在显著负相关(P<0.05,P<0.01,P<0.01,P<0.01)。
     清心培土法注重心脾动态制衡关系,强调清心法和培土法的共存。它在反映心脾药物消涨使用的同时,又强调泻心与健脾药物相辅相成的作用。
     结论
     禀赋不耐是特应性皮炎发病的根本原因,胎毒遗热是发病的主要诱因,心火旺、脾胃虚是其主导病机。
     中医药治疗特应性皮炎首先重视脾经,并关注脏腑之间的相互制衡关系。
     清心培土法是在特应性皮炎心脾病机的认识基础上而提出的治法,其蕴含的制衡策略尤其适用于复杂的病例存在心火脾虚交织互见的状况,具有自身的鲜明特色。
     第二部分临床研究
     目的
     评价特应性皮炎积分(SCORing AD,SCORAD)指数在评估特应性皮炎病情严重程度中的可靠性。
     在以往的研究基础上,开展清心培土法治疗特应性皮炎的近期和远期临床疗效评价。
     方法
     SCORAD指数内部相关性分析采用SCORAD指数评估特应性皮炎患者病情严重程度,分析SCORAD指数3个单项之间以及单项与总分之间的相关性。
     序贯试验以特应性皮炎评分指数(SCORAD)为疗效评价指标,采用序贯试验设计的方法评价清心培土方联合用药治疗特应性皮炎患者1月后的疗效。
     随访分析采用电话随访2005年2月—2007年10月在本院皮肤科门诊就诊的特应性皮炎临床确诊患者,随访者围绕基本痊愈、好转、无效三级病情详细询问患者或患者家属,总体评价清心培土法治疗特应性皮炎的远期疗效。
     结果
     SCORAD指数的皮损面积与皮损强度、SCORAD指数呈显著正相关(r分别为0.541,0.743;P<0.002,0.000)。皮损面积与主观症状无显著相关(r=0.296,P>0.05)。皮损强度与主观症状、SCORAD指数呈显著正相关(r分别为0.403,0.881;P<0.027,0.000)。主观症状与SCORAD指数呈显著正相关(r=0.704;P<0.000)。
     序贯试验试验至第7例患者时,试验线触及U界,说明清心培土方联合用药治疗特应性皮炎有效。
     随访分析共随访了18例患者,停药时间在3月—22月之间。结果基本痊愈5例,好转8例,无效5例,痊愈率27.78%,有效率72.22%。
     结论
     SCORAD指数在评估特应性皮炎病情中具有良好的内在一致性和可靠性。本研究运用SCORAD指数评估特应性皮炎病情取得了较好的效果。
     清心培土法为主,中西医结合治疗特应性皮炎的近期疗效肯定。以清心培土法为主的联合用药方案治疗特应性皮炎具有较好的远期疗效,在缓解病情,减少复发,减少外用激素和抗组胺药物用量方面发挥积极的作用。
     第三部分实验研究及临床意义分析
     目的
     近年来的研究进展认为天然免疫系统和调节性T细胞在特应性皮炎的发病机制中可能扮演重要角色,二者与Th1/Th2失衡存在密切的联系。本研究以血清IL-2/sIL-2R、TNF-α/sTNFR的状况,作为研究特应性皮炎患者CD4+CD25+调节性T细胞和天然免疫系统免疫状态的切入点。对特应性皮炎患者的免疫失调状况及其与?情的相关性进行探讨。还探讨了清心培土法干预后特应性皮炎患者免疫状况和病情的变化。
     方法
     采用酶联免疫吸附试验(ELISA)方法检测30例特应性皮炎患者及20例正常人血清中IL-2、sIL-2R、TNF-α、sTNFR水平。采用SCORAD指数评价患者病情严重程度,分析其与血清IL-2、sIL-2R水平、TNF-α、sTNFR的相关性。
     采用ELISA方法检测9例特应性皮炎患者治疗前后IL-2、sIL-2R、TNF-α及sTNFR的水平以及运用SCORAD指数评价病情的变化,进行自身前后比较,分析免疫指标与病情变化的相关性。
     结果
     与正常人对照组相比,特应性皮炎患者血清IL-2、TNF-α水平下降,但无显著差异(P>0.05),患者血清sIL-2R、sTNFR水平显著高于对照组(P<0.05,0.001)。患者血清sIL-2R水平的变化分别与皮损面积呈显著正相关(r=0.37,P<0.05),与患病时间呈显著负相关(r=-0.398,P<0.05)。患者血清TNF-α、sTNFR水平分别与SCORAD、患病时间无显著相关性(P<0.05)。
     9例特应性皮炎患者治疗前后比较,经治疗后IL-2、sIL-2R显著上升(P<0.05);经治疗后sTNFR、SCORAD积分显著下降(P<0.05);经治疗后的TNF-α升高,但差异无显著意义(P>0.05)。治疗后sTNFR与主观症状出现了显著相关性(P<0.05)。sIL-2R与病情的相关性增强,与皮损面积、主观症状、SCORAD均呈显著相关(P<0.05)。
     结论
     特应性皮炎患者sIL-2R升高与特应性皮炎的皮损面积和患病时间有关。特应性皮炎患者血清增高的sIL-2R可增加其中和IL-2的能力,导致免疫失调,在特应性皮炎病情活动或迁延过程中发挥作用。
     特应性皮炎患者血清高水平的sTNFR可加强其中和循环中的TNF-α的能力,继而引起TNF-α介导的抗感染和抗炎症反应能力下降,在AD的免疫发病机制中发挥作用。
     清心培土方联合用药治疗特应性皮炎可促进Th1型细胞因子IL-2增加,降低sTNFR水平,提高TNF-α的活性,缓解病情。
Since 1992,Sheehan etc.published a series of clinical randomized controlled trials in "Lancet" and "British Journal of Dermatology"about TCM (Traditional Chinese Medicine) treatments of atopic dermatitis which sugested TCM treatments may be effective on atopic dermatitis.From then on TCM treatments as a potential effective method of treatment was used for the clinical and experimental researchs of atopie dermatitis more and more.
     The effects and mechanisms of Qing-Xin-Pei-Tu therapy were researched from the points of view including literature studies of TCM treatments of atopic dermatitis,sequential trials and longer-term follow-up observations, as well as the immunological mechanisms in this paper.
     PartⅠLiterature studies
     Objective
     To explore the basic etiology and pathogenesis of atopic dermatitis. Analysis of the laws of TCM syndrome differentiation of atopic dermatitis. Explanation of Qing-Xin-Pei-Tu therapy which was a TCM treatment strategy of check and balance between Heart and spleen on atopic dermatitis.
     Methods
     According to historical literature analysis of the understanding of TCM on atopic dermatitis.According to history of medicine,combined with the characteristics and clinical features of atopic dermatitis,analysis of the leading pathogenesis and therapeutic methods.
     To collect published treatment literature of atopic dermatitis about Chinese herbal formula.Analysis of the laws on syndrome differentiation of atopic dermatitis by the methods combined with differentiation of Zang and Fu and the predictive diagnosis of syndromes by the effects of herbal prescription treatment.
     Results
     Etiology of atopic dermatitis was largely attributable to intolerance, ]eft heat and toxins during gestationa]period from Chinese medical viewpoint.
     The leading pathogenesis was cross-cutting between heart-fire and insufficiency of the spleen.Heart-fire could result in insufficiency of the spleen.Insufficiency of the spleen could result in heart-fire.A mixed situation was made by the cross-cutting between heart-fire and insufficiency of the spleen.
     Formulas of differentiation of symptoms and signs of atopic dermatitis were focused on the use of drugs for heart channel.Formulas of differentiation of disease were focused on the use of drugs for the liver channel.Formulas of Japanese Kampo treatment were focused on the use of drugs for pulmonary channel.The spleen channel was the most important target for therapy in all Formulas.There were significant negative correlations between heart and spleen,liver and spleen,liver and kidney,spleen and pulmonary separately (P<0.05,P<0.01,P<0.01,P<0.01).
     Qing-Xin-Pei-Tu therapy was focused on the relationship of check and balance between heart and spleen and emphasised on co-existence of Qing-Xin therapy and Pei-Tu therapy.At the same time,it also stressed that Jianpi drug and Xiexin drug were complimentary each other.
     Conclusions
     Etiology of atopic dermatitis was largely attributable to intolerance, left heat and toxins during gestational period.
     The leading pathogenesis was cross-cutting between heart-fire and insufficiency of the spleen.
     The spleen channel was the most important target for treatment of TCM on atopic dermatitis.
     Qing-Xin-Pei-Tu therapy was basic Chinese traditional treatment on atopic dermatitis with its own distinct characteristics..It is particularly suited to treat the complex cases accompanied with cross-cutting between heart-fire and insufficiency of the spleen.
     PaTtⅡClinical studies
     Objective
     To evaluate the reliability of SCORing Atopic Dermatitis index(SCORAD) for atopic dermatitis.To evaluate the short-term and long-term effect of combined therapies of traditional Chinese medicine and Western medicine on patients with atopic dermatitis.
     Methods
     The internal correlation analysis of SCORAD index:Evaluation of severity of the disease in patients with atopic dermatitis using SCORAD index and the internal correlation analysis of the three individual parts in SCORAD index as well as the correlation between the three individual parts and the total score.
     Sequential analysis test:The primary efficacy parameter was the SCORAD index.The effect was evaluated by Sequentialanalysis test after the patients had treated by combined therapies of traditional Chinese and Western medicine for one month.
     Follow-up analysis:Out-patients with atopic dermatitis were followed up by telephone who had visited dermatology department in our hospital during February 2005 to October 2007 period.Patients or patients' family members were asked about patients' condition in detail around three topic including basic recovery,improvement and invalid.The long-term effect of Qing-Xin-Pei-Tu therapy used for treatment on atopic dermatitis were evaluated on the whole.
     Results
     The internal correlation analysis of SCORAD index:The internal correlations between spread of lesions and intensity of lesions or SCORAD index were significantly(r=0.541,0.743 separately:P<0.002,0.000 separately). The internal correlations between spread of lesions and sujective symptom was not significantly(r=0.296,P>0.05).The internal correlations between sujective symptom and SCORAD index was significantly(r=0.704;P<0.000).
     Sequential analysis test:After the seventh petient had been treated,the effect of combined therapies of traditional Chinese and Western medicine was affirmed for patients with atopic dermatitis.
     Follow-up analysis:A total of 18 cases of patients with atopic dermatitis who had stopped treatment from 3 months to 22 months were followed up.As a result,5 cases cured,8 cases improved and 5 cases were invalid.Recovery rate was 27.78%.Effective rate was 72.22%.
     Conclusions
     SCORAD index was used for assessing the condition of atopic dermatitis with good internal consistency and reliability.SCORAD index was used for assessing the condition of atopic dermatitis in this study achieved good results.
     The short-term effect of combined therapies of traditional Chinese and Western medicine based on Qing-Xin-Pei-Tu therapy were affirmed for patients with atopic dermatitis.The therapeutic schedule had a good long-term effect and could help atopic dermatitis sufferers control their condition,reduce relapse,reduce the usage quantity of topical steroid and antihistamines.
     PartⅢExperimental study and analysis of clinical significance
     Objective
     Researches sugested that natural immune system and regulatory T cells might play an important role in atopic dermatitis pathogenesis in recent years.There were close relationship between Th1/Th2 polarization and natural immune system or regulatory T cells.In this study,serum interleukin-2(IL-2) and soluble interleukin-2 receptors(sIL-2R),tumor necrosis factor(TNF)-αand soluble tumor necrosis factor receptors(sTNFR) were detected as a entry point to study the immune status of CD4+CD25+ regulatory T cells and the natural immune system in patients with atopic dermatitis.The patient's immune disorders and their correlations with the patient's condition were discussed.To investigate the effective mechanisms of combined therapies of traditional Chinese and Western medicine on atopic dermatitis,the patients' conditions and the immune status changes were also discussed after the patients treated by combined therapies of traditional Chinese and Western medicine based on Qing-Xin-Pei-Tu therapy.
     Methods
     Serum IL-2 and slL-2R levels were detected by enzyme-linked immunosorbent assay(ELISA).The disease severity was assessed by SCORAD index.The relationships of IL-2 and slL-2R to SCORAD and course of disease were evaluated.
     SerumTNFαand sTNFR levels were detected by ELISA.The disease severity was assessed by SCORAD index.The relaLionships of TNF-αand sTNFR to SCORAD and course of disease were evaluated.
     Patients with atopic dermatitis were enrolled into this study before and after treated by combined therapies of traditional Chinese and Western medicine for one month.Serum IL-2,slL-2R,TNF-α,sTNFR levels were detected by ELISA.The disease severity was assessed by SCORAD index.
     Results
     30 patients with atopic dermatitis and 20 normal human controls were enrolled into this study.Before treatment,Serum IL-2 levels were decreased compared with the controls(P>0.05),while Serum sIL-2R levels were significantly increased in patients with atopic dermatitis(P<0.05).Serum sIL-2R levels showed a significant positive correlation with the spread of lesions and inverse correlation with course of disease(r=0.37 and -0.398 respectively;all P<0.05).
     30 patients with atopic dermatitis and 20 normal human controls were enrolled into this study.Before treatment,serum TNF-αlevels were mildly decreased compared with the controls(P>0.05),while Serum sTNFR levels were significantly increased in patients with atopic dermatitis(P<0.001).Serum sTNFR levels did not showed a correlation with the SCORAD and course of disease (all P>0.05).
     The state of illness were compared before and after treatment in 9 patients with atopic dermatitis.After treatment for one month,serum IL-2,slL-2R and SCORAD in patients in this study were significantly increased(P<0.05)and sTNFR levels significantly decreased compared with before treatment.The variable of TNF-αlevels no significantly difference(P>0.05).Serum sTNFR levels did not showed a correlation with the SCORAD and course of disease(all P>0.05).
     Conclusions
     The increased serum levels of sIL-2R in patients with atopic dermatitis had a positive correlation with the spread of lesions and negative correlation with course of disease.Elevated serum sIL-2R in patients with atopic dermatitis might increase the ability of binding IL-2 and lead to immune disorders.This mechanism might play a role in disorder of immune mechanism of atopic dermatitis or persistent activity of patient's condition.
     The increased serum levels of sTNFR in patients with atopic dermatitis might enhance the ability of binding TNF-αand reduce anti-infective and anti-inflammatory ability mediated by TNF-α.This mechanism might play a role in the pathogenesis of atopic dermatitis.
     The levels of Th1 type cytokines and the activity of TNF-αcould be promoted but the levels of sTNFR could be decreased by combined therapies of traditional Chinese and Western medicine based on Qing-Xin-Pei-Tu therapy.The therapeutic schedule was effective for patients with atopic dermatitis.
引文
[1]顾恒,尤立平,刘永生,等.我国10城市学龄前儿童特应性皮炎现况调查[J].中华皮肤科杂志,2004,37(1):29-31.
    [2]李晓青,洪建国.生命早期过敏体质形成及其影响因素[J].中华儿科杂志,2004,42(2):150-152.
    [3]Thomas Bieber.Atopic Dermatitis[J].NEngl J Med,2008,358(14):1483-1494.
    [4]李邻峰主编.特应性皮炎[M].北京:北京大学医学出版社,2006,第1版:6.
    [5]赵小燕,张学军,杨森.特应性皮炎发病机制的研究进展[J].国外医学皮肤性病学分册,2005,31(4):215-217.
    [6]Kevin D Cooper,康克非.银屑病和特应性皮炎免疫发病机制进展[J].中华皮肤科杂志,2007,40(9):520-523.
    [7]Szabo SJ,Kim ST,Costa GL,et al.A novel transcription factor,T-bet,directs Th1 lineage commitment[J].Cell,2000,100:655-669.
    [8]Leung DY,Boguniewicz M,Howell MD,et al.New insights into atopic derm atitis[J].J Clin Invest,2004,113:651-657.
    [9]Szabo SJ,Kim ST,Costa GL,et al.A novel transcription factor,T-bet,directs Th1 lineage commitment[J].Cell,2000,100:655-669.
    [10]Lee GR,Fields PE,Flavell RA.Regulation of IL-4 gene expression by distal regulatory elements and GATA-3 at the chromatin level[J].Immunity,2001,14:447 - 459.
    [11]李云秋,冯永.核因子κ B与Th细胞分化[J].医学临床研究,2006,23(2),277-279.
    [12]梁华平.王正国,朱佩芳.针对SIRS的新型抗炎靶点及抗炎策略研究进展-从炎症介质到核因子-κB[J].中国危重病急救医学,2001,13(11):649-652.
    [13]戴山林,姚欣,黄茂等.活化T细胞核因子转录因子家族在T细胞中的作用及与哮喘的关系[J].国际呼吸杂志,2007,27(1):33-36.
    [14]Braff MH,Gallo RL.Antimicrobial peptides:an essential component of the skin defensive barrier[J].Curr Top Microbiol Immunol,2006,306:91-110.
    [15]Trinchieri G,Sher A.Cooperation of Toll-like receptor signals in innate immune defence[J].Nat Rev Immunol,2007,7:179-190.
    [16]McGirt LY,Beck LA.Innate immune defects in atopic dermatitis[J].J Allergy Clin Immunol,2006,118:202-208.
    [17]Ong PY,Ohtake T,Brandt C,et al.Endogenous antimicrobial peptides and skin infections in atopic dermatitis[J].N Engl J med,2002,347:1151-1160.
    [18]Rieg S,Steffen H,Seeber S,et al.Deficiency of dermcidin-derived antimicrobial peptides in sweat of patients with atopic dermatitis correlates with an impaired innate defense of human skin in vivo[J].J Immunol,2005,174:8003-8010.
    [19]Howell MD,Gallo RL,Boguniewicz M,et al.Cytokine milieu of atopic dermatitis skin subverts the innate immune response to vaccinia virus[J].Immunity,2006,24:341-348.
    [20]陈巧英,李大金.CD4~+CD25~+调节性T细胞的生物学特性及功能[J].中国免疫学杂志,2007,23(1),89-92.
    [21]张莹,姚咏明,盛志勇.调节性T细胞研究进展[J].生理科学进展,2007,38(1):83-88.
    [22]Ziegler SF.FOXP3:of mice and men[J].Annu Rev Immunol,2006;24:209-26.
    [23]Ou LS,Goleva E,Hall C,Leung DY.Tregulatory cells inatopic dermatitis and subversion of their activity by superantigens[J].J Allergy Clin Immunol,2004,113:756-63.
    [24]Verhagen J,Akdis M,Traidl-Hoffmann C,et al.Absence of T regulatory cell expression and function in atopic dermatitis skin[J].J Allergy Clin Immunol,2006;117:176-83.
    [25]韩凌,项蕾红,郑志忠.调节T细胞及其在皮肤病中的作用[J].国际皮肤性病学杂志,2007,33(1):47-49.
    [26]莫秀梅.利湿散对湿热型湿疹患者临床症状影响的随机双盲对照试验[D].广州中医药大学硕士学位论文.2004.4.
    [27]林颖.特应性皮炎中医证候分类现状与辨证施治疗效的评价[D].广州中医药大学硕士学位论文 2005.4.
    [28]王欣.健脾渗湿法治疗特应性皮炎的疗效及对患者免疫功能调节的影响[D].广州中医药大学博士学位论文.2006,4.
    [29]孙晓冬.健脾渗湿冲剂治疗特应性皮炎的疗效及其对复发影响的评价[D].广州中医药大学硕士学位论文.2006,4.
    [30]陈达灿.培土清心方对特应性皮炎Th1/Th2细胞平衡及生存质量影响的研究[D].广州中医药大学硕士学位论文.2007.4.
    [31]廖勇梅.培土清心方治疗特应性皮炎的临床观察及作用机理初探[D].广州中医药大学博士学位论文.2007,4.
    [32]刘文静.培土清心方治疗特应性皮炎的疗效及对CC亚族趋化因子的影响[D].广州中医药大学博士学位论文.2007.4.
    [33]陈达灿,吴晓霞编著.特应性皮炎中西医结合治疗[M].北京:人民卫生出版社, 2008,第1版:1.
    [34]国家药典委员会.中华人民共和国药典(一部)[S],北京:化学工业出版社,2000:第7版.
    [35]江苏新医学院.中药大辞典[M].上海:上海人民出版社,1977:第1版.
    [36]国家中医药管理局中华本草编委会.中华本草精选本[M].上海:上海科学技术出版社,2002:第1版.
    [37]全国中草药汇编编写组.全国中草药汇编[M].北京:人民卫生出版社,1978:第1版.
    [38]顾伯康,陈荣荣.辨证治疗素质性湿疹70例[J].重庆中医药杂志.1988(1):6-7.
    [39]吕飞,周春燕.辨证治疗异位性皮炎[J].中国民间疗法.2004,12(6):8-9.
    [40]安家丰,张志礼.儿童异位性皮炎中医药治疗研究[J].皮肤病与性病.1996,18(1):42-44.
    [41]李正才.分型辨治特应性皮炎[J].辽宁中医杂志,2003,30(1):911-912.
    [42]黄咏菁,陈达灿,莫秀梅.健脾渗湿冲剂治疗儿童异位性皮炎脾虚证的临床观察[J].陕西中医,2004(5):396-198.
    [43]朱金土,余土根,曹毅.皮炎消净饮1号治疗湿热型异位性皮炎的临床研究[J].浙江中西医结合杂志,2003,13(6):342-343,349.
    [44]林珠.清热利湿法治疗异位性皮炎36例[J].北京中医,1996(4):34.
    [45]王文革.汪受传教授治疗异位性皮炎的经验[J].中华中医药杂志,2008,23(8):703-704.
    [46]秦万章.先天性过敏性湿疹的证治[J].中国中西医结合杂志,2008,28(8):677-678.
    [47]陈妙善.异位性皮炎的辨证论治[J].上海中医药杂志,1987(11):17.
    [48]范瑞强.异位性皮炎诊疗体会(附52例病例分析)[J].新中医,2006,38(6):79-80.
    [49]郑益志.余土根治疗异位性皮炎的经验[J].浙江中医杂志,2005(2):54-56.
    [50]李林.在英国用中药治疗异位性湿疹115例临床观察[J].甘肃中医,1994,7(11):11-13.
    [51]刘俐丽.张作舟教授治疗异位性皮炎的经验[J].中国社区医师,1988(1):34.
    [52]邢有兰,李欢,龚华,等.中西医结合治疗成人特应性皮炎的临床观察[J].中国麻风皮肤病杂志,2006,22(11):954.
    [53]刘源,叶秋华,陈加媛,等.中西医结合治疗儿童特应性皮炎临床研究[J].南京中医药大学学报,2007,23(2):93-95.
    [54]史永俭,张春敏,马冬梅,等.中西医结合治疗特应性皮炎的临床观察[J].中国中西医结合杂志,2008,28(8):686-688.
    [55]郑继达,刘广和.中西医结合治疗异位性皮炎36例[J].广西中医药,1996,19(2):15-16.
    [56]申素萍,陈培新.中药辨证治疗异位性皮炎65例临床观察[J].中医药研究,1997,13(6):21-22.
    [57]刘玉梅.中药为主治疗伴发支气管哮喘的异位性皮炎44例[J].1993(8):25.
    [58]付宏伟.中药治疗婴儿期异位性皮炎160例[J].中国中医药信息杂志,2000,7(2):66.
    [59]钟卫红.中医辨证治疗特应性皮炎疗效观察[J].中医药学报,2002年,30(1):26-27.
    [60]任众.中医辨证治疗异位性皮炎32例体会[J].甘肃中医,2005,18(9):25-26.
    [61]张林.中医辨证治疗异位性皮炎1100例[J].四川中医,2003,21(12):76.
    [62]周海啸.中医辨证治疗异位性皮炎临床观察[J].中国中医药信息杂志,2000,7(10):52-53.
    [63]姚春海.中医辨治特应性皮炎体会[J].中国中西医结合杂志,2008,28(8):682.
    [64]李元文,张丰川,周德瑛.辨证治疗特应性皮炎35例[J].北京中医药大学学报,2002.25(5):69-70.
    [65]周双印.辨证治疗异位性湿疹31例报告[J].中医杂志,1989(12):36-38.
    [66]喻桃,陈保疆,王萍,等.健脾补肾疗法对特应性皮炎患者血清总IgE水平的影响[J].吉林中医药,2006,26(9):15-17.
    [67]李菲,罗文辉.中西医结合治疗特应性皮炎44例总结[J].湖南中医杂志,2006,22(4):20-21.
    [68]孙晓冬.陈达灿教授从心脾论治特应性皮炎经验谈[J].中国中西医结合皮肤性病学杂志,2006,5(1):55-56.
    [69]孙剑虹,徐串联.滋阴除湿方治疗异位性皮炎43例[J].中国中医药科技,2006,13(6):436-437.
    [70]关丽霞,栗庆林.自拟活血祛风汤治疗特应性皮炎68例临床观察[J].长治医学院学报,2006,20(4):302-303.
    [71]麻林玖,梁红梅.加味启脾丸颗粒治疗儿童特应性皮炎疗效观察[J].中国皮肤性病学杂志,2006,20(11):698.
    [72]陈艺明,林金宝,黄海松,等.滋阴熄风汤治疗特应性皮炎临床疗效观察[J].2006,35(1):55-56.
    [73]杨瑛,孙继兰,王麦娣,等,健脾止痒颗粒治疗特应性皮炎临床观察[J].中国皮肤性病学杂志,2005,19(12):755-756.
    [74]李忻红,田静.补肾养血煎剂治疗儿童特应性皮炎疗效观察[J].2004,11(11):999.
    [75]胡爽杨.刘公望教授针药并用治疗异位性皮炎经验[J].上海针灸杂志,2006,25(4):1-2.
    [76]姚守恩,周渐云.许铣治疗异位性皮炎经验[J].实用中医药杂志,2006,22(2):116.
    [77]车武.四虫止痒汤治疗成人异位性皮炎62例[J].承德医学院学报,2005,22(1):38-39.
    [78]阮劲峰,谢汝汉.四物汤加减治疗32例儿童异位性皮炎的疗效[J].现代医院,2004,4(6):73-74.
    [79]李丰.异功散合秦艽丸治疗儿童异位性皮炎14例[J].2003,22(5):34.
    [80]周智敏.中西医结合治疗异位性皮炎41例临床研究[J].湖南中医药导报,2003,9(3):34-35.
    [81]吕会玲.当归生地黄方治疗异位性皮炎31例[J].山东中医杂志,2002,21(8):474.
    [82]魏跃钢,单敏洁.小儿化湿汤加减治疗异位性皮炎42例[J].南京中医学院学报,1993,9(3):52.
    [83]刘汉长.特应性皮炎的中医治疗探讨[J].华夏医药,2005(3):208-209.
    [84]尤立平,刘永生,杨顶权,等.44例特应性皮炎中医临床证候分析与辨证治疗[J].中国中西医结合皮肤性病学杂志,2003,2(2):71-73.
    [85]刘天骥,吴积华.养血祛风汤治疗异位性皮炎60例[J].四川中医,1998,16(9):29.
    [86]段行武,孙凤琴.健脾养血活血法治疗异位性皮炎97例[J].河北中医,1998,20(4):223.
    [87]董子亮,陈木森,菊池,等.奇妙饮治疗遗传过敏性皮炎临床观察[J].中国中医药信息杂志,1997,4(12):36-37.
    [88]王长海,王琦,张仲海.中西医结合治疗儿童期异位性皮炎[J].实用中西医结合杂志1997,10(9):835.
    [89]曾昭明,潘伟军.中药内服外用治疗异位性皮炎47例[J].新中医,2007,39(3):56-57.
    [90]万顺泉.中药内外合治遗传过敏性皮炎18例[J].湖南中医药导报,1997,3(4):58-59.
    [91]邹铭西.湿疹治疗宜辨证辨病相结合[J].中国中西医结合杂志,2008,28(8):680-681.
    [92]卜静波,李冰玲.四物汤加味配合外洗治疗异位性湿疹42例[J].实用中医内科杂志,2003,17(1):49.
    [93]张漓娟,蒋靖.中西医结合治疗异位性皮炎的临床观察[J].现代中西医结合杂志, 2000,9(8):708.
    [94]王琳.90例异位性皮炎的临床研究[J].中国中西医结合皮肤性病学杂志,2003,2(1):46-47.
    [95]关小红,芦彩慧.消风导赤汤治疗儿童异位性皮炎50例[J].辽宁中医杂志,2000,27(6):264.
    [96]倪文琼,丁巍,于江亭.三组药物治疗异位性皮炎前后血清IL-4和总IgE的临床研究[J].河南诊断与治疗杂志,2000,14(3):174-175.
    [97]李斌.蜈蚣方治疗异位性皮炎31例[J].吉林中医药,1999(4):25.
    [98]斋藤隆,郭佩玲,吕齐,等.中药治疗特异变应性皮炎106例临床总结[J].中国医药学报,1997,12(1):34-37.
    [99]林颖,陈达灿,莫秀梅.特应性皮炎中医证候分类现状与辨证施治疗效的评价[J].中国中西医结合皮肤性病学杂志,2005,4(4):266-271.
    [100]Sheehan MP,Atherton DJ.A controlled trial of traditional Chinese medicinal plants in widespread non-exudative atopic eczema[J].British Journal of Dermatology 1992;126(2):179-84
    [101]Sheehan MP,Atherton DJ.One-year follow up of children treated with Chinese medicinal herbs for atopic eczema[J].British Journal of Dermatology 1994;130(4):488-93
    [102]Sheehan MP,Rustin MH,Atherton DJ,et al.Efficacy of traditional chinese herbal therapy in adult atopic dermatitis[J].Lancet 1992;340(8810):13 - 17.
    [103]Latchman Y,Banerjee P,Poulter LW,,et al.Association of immunological changes with clinical efficacy in atopic eczema patients treated with traditional chinese herbal therapy(zemaphyte)[J].Int Arch Allergy Immunol 1996;109(3):243-9.
    [104]Fung AY,Look PC,Chong LY,But PP,Wong E.A controlled trial of traditional Chinese herbal medicine in Chinese patients with recalcitrant atopic dermatitis[J].Int J Dermatol 1999;38(5):387-92.
    [105]Hon K,Leung TF,Wong Y,et al.A pentaherbs capsule as a treatment option for atopic dermatitis in children:an open-labeled case series[J].American Journal of Chinese Medicine 2004;32(6):941-50.
    [106]Hon KL,Leung TF,Ng PC,,et al.Efficacy and tolerability of aChinese herbal medicine concoction for treatment of atopic dermatitis:a randomized,double-blind,placebo-controlled study[J].Br J Dermato],2007,157(2):357-63.
    [107]Kobayashi H,Mizuno N,Teramae H,etal.Diet and Japanese herbal medicine for recalcitrant atopic dermatitis:efficacy and safety[J].Drugs Exp Clin Re,2004,30(5-6):197-202.
    [108]Hiromi Kobayashil,Masamitsu Ishiil,Satoshi Takeuchi,et al.Efficacy and Safety of a Traditional Herbal Medicine,Hochu-ekki-to in the Long-term Management of Kikyo(Delicate Constitution)Patients with Atopic Dermatitis:A 6-month,Multicenter,Double-blind,Randomized,Placebo-controlled Study[J].Evidence-based Complementary and Alternative Medicine(eCAM),2008(1):1-7.
    [109]Salameh F,Perla D,Solomon M,etal.The effectiveness of combined Chinese herbal medicine and acupuncture in the treatment of atopic dermatitis[J].J Altern Complement Med,2008,14(8):1043-8.
    [110]Hiromi Kobayashi,Kuniaki Wakahashi,aobuyuki Mizuno,et al.An Alternative Approach to Atopic Dermatitis:Part Ⅱ-Summary of Cases and Discussion[J].Evidence-based Complementary and Alternative Medicine (eCAM),2004;1(2) 145-155.
    [111]Armstrong N C,Ernst E.The treatment of eczema with Chinese herbs:a systematic review of randomized clinical trials[J].British Journal of Clinical Pharmacology 1999;48(2):262-264
    [112]C Hoare,A Li Wan Po,HHanifin和Rajka.Systematic review of treatments for atopic eczema[J].Health Technology Assessment,2000,4(37):1-197
    [113]Zhang W,Leonard T,Bath-Hextall F,et al.Chinese herbal medicine for atopic eczema[J].Cochrane Database of Systematic Reviews 2005(4).
    [114]刘建平.循证医学方法与中医疗效评价[J].首都医科大学学报.2007,28(2):212-215.
    [115]陈达灿,吴晓霞编著.特应性皮炎中西医结合治疗[M].北京:人民卫生出版社,2008,第1版:39-40.
    [116]Kunz B,Oranje AP,Labreze L,et al.Clinical validation and guidelines for the SCORAD index:consensus report of the European Task Force on Atopic Dermatitis[J].Dermatology.1997,195:10-19.
    [117]N.Pucci,E.Novembre,M.G.Cammarata,et al.Scoring atopic dermatitis in infants and young children:distinctive features of the SCORAD index[J].Allergy 2005:60:113-116.
    [118]Charman C,Hanifin,Rajka H.Outcome measures of disease severity in atopic eczema[J].Arch Dermatol 2000;136:763-769.
    [119]鞠梅,陈昆,常宝珠,等.曲尼司特胶囊治疗特应性皮炎的多中心随机双盲对照 研究[J].中华皮肤科杂志,2007,40,(1):38-11.
    [120]贺石林,陈修.医学科研方法导论[M],北京:人民卫生出版社,1998,第1版:224-225.
    [121]徐端正.医学序贯试验[M].上海:上海科学技术出版社,1979,第1版:55-68.
    [122]金丕焕.医用统计方法[M].上海:上海医科大学出版社,1993,第1版:28.
    [123]李润祥,朱慧兰,樊翌明,等.他克莫司软膏治疗特应性皮炎疗效和安全性评价[J].临床皮肤科杂志,2007,36(12):757-760.
    [124]Hans Dooms,Estelle Kahn,Birgit Knoechel,et al.IL-2 Induces a Competitive Survival Advantage in T Lymphocytes[J].The Journal of Immunology,2004,172:5973-5979.
    [125]Calogero Caruso,Giuseppina Candore,Diego Cigna,et al.Biological significance of soluble L-2 receptor[J].Mediators of Inflammation,1993,2:3-21.
    [126]Thomas Hehlgans,Klaus Pfeffer.The intriguing biology of the tumour necrosis factor/tumour necrosisfactor receptor superfamily:players,rules and the games[J].Immunology,2005,115:1-20.
    [127]Kapp A,Neuner P,Krutmann J,etal.Production of interleukin-2 by mononuclear cells in vitro in patients with atopic dermatitis and psoriasis.Comparison with serum interleukin-2 receptor levels[J].Acta Derm Venereol,1991,71(5):403-6.
    [128]Rubin LA,Kurman CC,Fritz ME,et al.Soluble interleukin 2 receptors are released from activated human lymphoid cells in vitro[J].J Immunol.1985,135(5):3172 - 3177.
    [129]K.N.Lai.Correlation between cellular interleukin 2 receptor(IL2R)expression,Soluble interleukin 2 receptor(sIL-2R)production,and interleukin 2 release in healthy sunjects and various immunological diseases[J].J Hong Kong Med Assoc,1991,43(3) 146-149.
    [130]Michael S.Loughnan,Colin J.Sanderson,G.J.V.Nossal.Soluble interleukin 2 receptors are released from the cell surface of normal murine B lymphocytes stimulated with interleukin 5[J].Proc.Natl.icad.Sci.USA,1988,85:3115-3119.
    [131]Howell MD,Novak N,Bieber T,et al.Interleukin-10 downregulates anti-microbial peptide expression in atopic dermatitis[J].J Invest Dermatol,2005 Oct:125(4):738-45.
    [132]Ichiro Nomura,Elena Goleva,Michael D.Howell,et al.Cytokine Milieu of Atopic Dermatitis,as Compared to Psoriasis,Skin Prevents Induction of Innate Immune Response Genes[J].The Journal of Immunology,2003,172(9):39,62-3269.
    [133]朱学军,曹雪涛.肿瘤坏死因子受体研究新进展[J].生理科学进展,1994,25(2):117-120.
    [134]Marcel Flendriel,Wynand HPM Vissers2,Marjonne CW Creemersl,et al.Dermatological conditions during TNF-α-blocking therapy in patients with rheumatoid arthritis:a prospective study[J].Arthritis Research & Therapy,2005,7:666-676。

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