清心培土法治疗特应性皮炎的疗效及对患者免疫调节作用的研究
详细信息    本馆镜像全文|  推荐本文 |  |   获取CNKI官网全文
摘要
背景
     引起特应性皮炎(AD)的众多因素中,以免疫异常为中心环节的发病机制网络已成为中西医研究热点,导师陈达灿教授创立了清心培土法治疗AD,疗效确切。本研究在既往的临床研究已证实该法有效的基础上,进一步观察其疗效并检测血清总IgE、白介素(IL-5)、白介素(IL-12)和白介素(IL-13)的变化,以探讨清心培土法治疗AD的可能机制,为AD的规范化治疗提供依据。
     目的
     1.检测AD患者血清总IgE和IL-5、IL-12和IL-13的表达,以进一步深入认识AD的病机。
     2.以清心培土法治疗AD,观察治疗前后AD患者SCORAD积分的变化,以评价导师的经验方清心培土方对AD的疗效。
     3.用ELISA法检测治疗前及治疗3个月后血清总IgE、IL-5、IL-12、IL-13水平,并与正常组进行对照,以探讨清心培土法治疗特应性皮炎可能的机制,为AD的规范化治疗提供依据,有利于中医治疗本病的临床推广和科学性的认证,并为新药开发奠定一定的基础。
     方法
     本研究纳入19例符合标准的AD患者为研究对象,于治疗前及治疗后3个月时分别记录SCORAD积分,并在治疗前及治疗后3个月时,采用ELISA法检测血清总IgE和IL-5、IL-12、IL-13的水平,以19例健康志愿者为对照。
     结果
     1.临床疗效观察
     本临床观察共纳入19例符合标准的AD患者,内服中药清心培土方,临床随证加减,以SCORAD指数进行评价,结果显示治疗前的SCORAD评分为46.16±16.94,治疗3个月后为33.53±16.31,较治疗前降低,差异有统计学意义(P<0.05),说明清心培土法治疗AD有良好的疗效。
     2.血清总IgE的测定
     AD患者治疗前血清总IgE为1.1±0.84μg/ml,较健康对照组0.25±0.07μg/ml为高,差异有统计学意义(P<0.01);治疗后AD组血清总IgE为0.63±0.69μg/ml,较治疗前降低,差异有统计学意义(P<0.05)。
     3.血清IL-5的测定
     AD患者治疗前血清IL-5为1.12±0.78ng/ml,较健康对照组0.49±0.23 ng/ml为高,差异有统计学意义(P<0.05);治疗后AD组IL-5为0.81±0.71ng/ml,较治疗前降低,差异有统计学意义(P<0.05)。
     4.血清IL-12的测定
     AD患者治疗前血清IL-12为0.82±0.78ng/ml,较健康对照组1.17±1.00 ng/ml为低,差异无统计学意义(P>0.05);治疗后AD组IL-12为1.00±0.91ng/ml,较治疗前升高,差异无统计学意义(P>0.05)。
     5.血清IL-13的测定
     AD患者治疗前血清IL-13为0.12±0.27ng/ml,较健康对照组0.13±0.02 ng/ml为低,差异无统计学意义(P>0.05);治疗后AD组IL-13为0.12±0.03 ng/ml,较治疗前为低,差异无统计学意义(P>0.05)。
     结论
     1.清心培土法治疗AD能显着降低患者的SCORAD指数,说明疗效确切。
     2.清心培土法治疗AD可显着降低患者血清总IgE和Th2型细胞因子(IL-5)的水平,从而调整Th1/Th2型细胞因子的平衡失调,推测这可能是其作用机理之一。
Objectives
     1. Investigating the mechanism of Atopic Dermatitis (AD) more deeply through measuring IgE、IL-5、IL-12 and IL-13 of the patients with AD.
     2. Observe changes of the scores of SCORAD index before treatment and 3 months after treatment of the formula, to value therapeutic effect of advisor's formula of clearing away heart-fire and hilling.
     3. Measuring IgE, IL-5, IL-12andIL-13of the patients with AD using the ELISA technique before and after the treatment for 3 months respectively. Then compare with 19 healthy controls, in order to investigate the possible mechanism of treatment. It is good for finding its possible mechanism to direct our clinical practice and to make basis of the development of new Traditional Chinese medicine.
     Method
     19 patients diagnosed atopic dermatitis are selected to this clinical trial. Scores of SCORAD index are collected before treatment and 3 months after treatment respectively. The level of IgE、IL-5、IL-12 and IL-13 in the serum of both the patients and health controls were detected by ELISA. Results
     1.19 patients diagnosed atopic dermatitis were admitted to the clinical trial and treated with formula of the clearing away heart-fire and hilling. According to evidence to adjust Chinese herb. SCORAD scale was used to evaluate clinical therapeutic effect. After treatment, scores of SCORAD index decline. So it is demonstrates that the method of clearing away heart-fire and hilling is used to AD patients.
     2. Before treatment, IgE in serum of the patients was higher than those of the healthy controls (P<0.01), compared with those before treatment. IgE had much change after treatment (P<0.05).
     3. The value of IL-5 before treatment of AD patients was more than that of healthy people. The statistic significance was also demonstrated (P< 0.05). After treatment of the formula of clearing away heart-fire and hilling, the value of level of IL-5 after treatment was lower than that before treatment with statistical significance (P< 0.05).
     4. The level of IL-12 of AD patients before treatment was lower than that healthy people. The difference is statistically significant (P> 0.05). After treating with the formula of clearing away heart-fire and hilling, the value of IL-12 arised with statistical significance (P>0.05).
     5. The values of IL-13 among healthy people, before treatment and after treatment are nearly the same (P>0.05).
     Conclusions
     1. After treating with formula of the clearing away heart-fire and hilling, the scores of SCORAD index decline. So it is demonstrates that the formula of clearing away heart-fire and hilling is used to AD patients.
     2. Treatment with the formula of clearing away heart-fire and hilling, the level of the IgE was decreased (P<0.05), we speculate that it may be one of therapy mechanism of AD.
     3. After treating with formula of the clearing away heart-fire and hilling,the level of IL-5 declined (P<0.05), the level of IL-12 increased (P>0.05), we speculated that the unbalance of expression of Thl/Th2 cytokines was improved.
引文
[1]王侠生,廖康煌,杨国亮.皮肤病学[M].上海:海科学技术文献出版社,2005,395-396.
    [2]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):56-56.
    [3]陈达灿,刘炽.特应性皮炎的禀赋发病因素和心脾病机的理论与实践[J].新中医,2009,41(8):7-8.
    [4]Larsen FS, Holm NV, Hennmgsen K.Atopic dermatitis, Agenetic-epidermiol study in a population-basal twin sample[J]. JAm Acad Dermatol.1986, 15(3):487-494.
    [5]黄泰康.中医皮肤病性病学[J].中国医药科技出版社,2000,222-226.
    [6]李元文,张丰川,周德瑛.辨证治疗特应性皮炎[J].北京中医药大学学报,2002,25(5):69-70.
    [7]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.
    [8]张芃,王萍.张志礼治疗异位性皮炎经验[J].中医杂志,1998,39(7):402-403.
    [9]郭佩玲.异位性皮炎恶化的中医治疗[J].中国医药学报,2002,17(9):561-562.
    [10]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,2004,25(5):396-398.
    [11]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].中国中医药信息杂志,2004,11(11):999-1000.
    [12]郎娜,姚春海,柏燕军等.参归煎剂合湿毒膏治疗血虚风燥型特应性皮炎[J].中国中西医结合皮肤性病学杂志,2007,6(1):22-23.
    [13]莫秀梅,黄咏菁,陈达灿,池凤好.利湿散冲剂治疗慢性湿疹的疗效及对血清总IgE水平的影响[J].中国中西医结合皮肤性病学杂志,2004,3(1):25-26.
    [14]李东海,眭道顺,刘靖等.健脾祛风法治疗特应性皮炎疗效观察[J].吉林中医药.2006,26(8):18-19.
    [15]李斌.蜈蚣方治疗异位性皮炎31例[J].吉林中医药,1999,19(4):52.
    [16]陈学荣,张倩,韩春雷等.苦参及生物碱对敏性皮肤病的临床及实验研究[J].医学研究通讯,1999,28(11):15-16.
    [17]蔡永敏,任玉让.王黎.最新中药药理与临床应用[J],北京华夏出版社,1999,188-190:426-433.
    [18]王汉涛.云苓多糖对小鼠产生细胞因子的促进作用[J],1993,28(10):722.
    [19]李铁民,梁再斌.甘草甜素免疫作用研究进展[J].中草药,1995,24(10):553.
    [20]蔡永敏,任玉让,王黎.最新中药药理与临床应用[M].北京华夏出版社,1999:234.
    [21]陈文展,黛连油膏治疗异位性皮炎6例[J].福建医药杂志,2003,25(3):224-225
    [22]刑守平,安改香.苦冰酊止痒效佳[J].中国民间疗法,1999,7(3):44.
    [23]张芃,王萍.张志礼治疗AD经验[J],中医杂志,1998,39(7):402-404.
    [24]张璃涓,蒋靖.中西医结合治疗异位性皮炎的临床观察[J].现代中西医结合志,2000,9(8):708-709.
    [25]喻桃,陈保疆,王萍.健脾补肾法对特位性皮炎患者血清总IgE水平的影响[J].吉林中医药,2006,26(9):15-16.
    [26]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.
    [27]陈达灿.吴晓霞,特应性皮炎中西医诊断与治疗[M].人民卫生出版社,2008:3.
    [28]陈可.穴位注射治疗性皮炎例[J].上海针灸杂志,2004,23(6):25-26.
    [29]王笃金。隔药饼灸治疗异位性皮炎20例[J].中国针灸,2000,25(10):216.
    [30]Vendre RB. Alternative treatments for atopic dermatitis selected review [J].Skin herapy Lett,2002,7(2):1.
    [31]Yuan R, linY. Trandtional Chinese medicine:an approach to scientific ptoof and clinical validation [J] Pharmacol Ther,2000,86(20):191
    [32]Leung DY. Pathogenesis of atop ic dermatitis[J]. JA llergy ClinImmuno 1,1999,104(Suppl):S99-S108.
    [33]Parnia S, F rew AJ. Chemokines and atopic dermatitis[J]. J Allergy Clin Immanol,2000,105:892-894.
    [34]Baldacci Modena P CarrozziL, et al. Skin prick test reactivityto common acroallergens in reaction to total IgE, respiratory symptoms, and smoking in ageneralpopulation sample of northern Italy [J]. Allergy,1996,51: 149-156.
    [35]Novak N, Valenta R, Bohle B, et al. FcepsilonRI engagement ofLangerhans cell-like dendritic cells and inflammatory dendritic epi2dermal cell-like dendritic cells induces chemotactic signals and different T-cell phenotypes in vitro[J].J Allergy Clin Immunol,2004,113(5):949-957.
    [36]Bunikowski R, Mielke M, Skarabis H, et al. Prevalence and roleof serum IgE antibodies to the Staphylococcus aureus-derived su2 erantigens SEA and SEB in children with atopic dermatitis [J].JAllergy Clin Immunol,1999,103(1 Pt 1):119-124.
    [37]Hauk PJ, Hamid QA, Chrousos GP, et al. Induction of corticos2teroid insensitivity in human PBMCs by microbial superantigens[J]. J Allergy Clin Immunol,2000,105(4):782-787.
    [38]Robert C,Kupper TS. Inflammatory skin diseases, T cells, and immune surveill[J].AnceN Engl J Med,1999,341 (24):1817-1828.
    [39]Lindborg M, Magnusson CG, Zargari A, et al. Selective cloning of allergens from the skin colonizing yeast Malassezia furfur by phagesurface display technology[J].J Invest Dermatol,1999,113 (2):156-161.
    [40]Till SDickason R, Huston D, etal. IL-5 secretion by allergen. Stimulated CD4+ T cells in primary culture:relationship to exp ression of allergic disease. J Allergy Clin Immunol,1997,99(4):563-569.
    [41]Walker C, Checkel J, Cammisuli S. et al. IL-5 production by NK cells contributes to eosinophil infiltration in a mouse model of allergic inf lammation [J]. Immunol,1998,161(4):1962-1969.
    [42]Barata LT, Ying S, MengQ, etal. IL-4 and IL-5-positive Tlymphocytes, eosinophils, and mast cells in allergen-induced late-phase cutaneous reactionsin atopic subjects[J]. Allergy Clin Immunol,1998,101 (Pt 1):222-230.
    [43]Julius P, Hochheims D, Poser K, et al. lnterleukin-5 recepters on human lung eosinophils after segmental allergen challenge[J]. Clin Exp Allergy,2004,34:1064-1070.
    [44]Lampinen M, Carlson M, Hakansson LD, et al. Cytokineregulated accumulation of eosinophils in inflammatory disease[J]. Allergy,2004,59: 793-805.
    [45]王美琴,自春学,钮善福.白介素-5与支气管哮喘的治疗[J].国外医学内科学分册,2000,27(3):93.
    [46]Teran LM. Chemokine and IL-5:major player of eosinophil receitment in asthma[J]. Clin Exp Allergy,1999,29:287-290.
    [47]Akdis CA. Akdis M, Trautmann A. et al. Immune regulation in atopic dermatitis[J]. Curt Opin Imnlunol,2000,12(6):641-646.
    [48]Julius P, Hochheims D, Poser K, et al. lnterleukin-5 recepters on human lung eosinophils after segmental allergen challenge[J]. Clin Exp Allergy, 2004,34:1064-1070.
    [49]Lampinen M, Carlson M, Hakansson LD, et al. Cytokineregulated accumulation of eosinophils in inflammatory disease[J]. Allergy,2004,59:793-805.
    [50]Spergel JM. Mizoguchi E, Oeugen H el Roles of Thl and Th2 cytokines in a murine model of allergic dermalifis[J]. Clin Invest,1999.103:1103-1111.
    [51]Novak N, Valenta R, Bohle B, Laffer S, Haberstok J, Kraft S, ct, al. FcepsilonRl engagement of Langerhans cell ike dendritic cells and inflammatory dendritic epidermal cell like dendritic cellsinduces chemotactic signals and diferent T cell phenotypes in vitro[J]. J Allergy Clin hnmunol,2004,113(5):949-957.
    [52]Teraki Y, Hotta T, Shiohara T. Increased circulating skin-homing cu-taneous 1 mphoeyte-associated antigen(CLA)+ type 2 cytokine-producing cells, and decreased CLA+ type 1 cytokine-producing cells in atopic dermatitis [J]. Br J Dennatol,2000,143(2):373-378.
    [53]Hitoshi Y, Yamaguchi N, Korenaga M, et al. In vivo administration of antibody to murine IL-5 receptor inhibits eosinophilia of IL-5 transgenic mice[J]. lnt lmmunol,1991,3(2):135-139.
    [54]Stem A5. Bonhomme Aguenounou M, Purification to homogenenty and partial charactenzation of cytotoxic lympnocyte mathration factor from human B-lmmploblastion cells[J], Proc Natl Acad Sci USA 1990,7:808-6812.
    [55]Brumda MJ,Muller G Garely M. Role of IL-12 an anti-tumour agent[J]Leuk Bowl,1994,55:286-290.
    [56]Aiba S, Manome H, Yoshino Y, Tagami H. Alteration in the production of 1L-10 and 1L-12 and aberrant expression of CD23, CD83 and CD86 hv monocytes or monocyte-derived dendritic cells from atopic dermatitis patients[J]. Exp Dennatol,2003,12(1):86-95.
    [57]Hasko G. Kuhel DG. Chen JF. et al.Adenosine inhibits IL-12 and TNF alphalproduction via adenosine A2a receptor dependent and independent mechanisms[J]. Clin Invest,1998,101(1):252.
    [58]Hasko G. Juhel DG, Salzman AL. et al. ATP suppression of interleukin-12 and turnour necrosis factor-alpha release from macrophage. s. Br[J] Pharmaeol, 2000,129(5):909.
    [59]Salkowski CA, Thomas KE. Cody MI. et al. Impaired IFN regulatory factor-1 knockout mice during endotoxemia is secondary to a loss of both IL-12 and lL-12 receptor experession. [J]Immunol,20001; 165(7):3970.
    [60]Sabita R. Richard C. Kelley C. et al. Deficiency of the transcription factors increases lipopolysacch-cride-induced macrophage interleukin 12 procuction [J]. Srugery.1999,126:239.
    [61]Tsunemi Y, Saeki H, Nakamura K, Sekiya T, Hirai K, Fujita H, et al. lnterl-ukin-12[IL-12]-untranslated region polymorphism is associated with susceptibility to atopic dermatitis and psoriasis、ulgaris[J]. Demlatol Sci, 2002,30(2):161166.
    [62]Miriam W, Vivi-ann L, Petra S。et al. Suppressionn of inter-leukin-12 production by human monocytes after preincubation with lipopoly sacchafide [J]. Blood,1999,94(5):1717.
    [63]Hida N, Shimoyarna T, Neville P, et al. Increased expression of IL-10. IL-12(P40)mRNA in Helicohacter pylori infected gastric mucosa:relation to bacterial cag status and peptic ulceration[J]. Clin Pathol.1999; 52:658.
    [64]Trinchieri G, Scott P. The role of interleukin 12 in the immune response. disease and therapy[J]. Immunol,1994,15:460.
    [65]XuX. Sumita K. FengC, et al. Down-regularion of IL-12 p40 gene in plasmodium berghei-infected mice. [J]Immunol,2001; 167(1):235.
    [66]Shea JJ, Gadina M, Schreiber RD. Cytokines signaling in 2002:new surprise in the JAK/STAT pathway[J]. Cell,2002,109(Suppl):5121.
    [67]Habu Y, Seki s, Takayama E, et al. The mechanism of a defective IFN-gam ma response to bacterial toxins in an atopic dermatitis model, NC/Nga mice, and the therapeutic efect of IFNgamma, IL-12, or IL-18 on dermatitis [J]. lmmunol,2001,166(9):5439-547.
    [68]Park WR, Park CS, Tomura M, CD28 costimulation is required not only to induce IL-12 receptor but also torender janus kinases/STAT4 responsive to IL-12 stimulation in TCR-triggered T cells[J]. Eur J Immunol,2001,31(5): 1456-64.
    [69]Visconti. R. etc, Importance of the MKK6/p38 pathway for interleukin-12 induced A serine phosphorylation and transcriptional activity[J]. Blczxt, 2000,96(5):1844-52.
    [70]Gorbacher AV. IL-12 augments CD8+T cell development for contact hypersensitivity responses and circumvents anti-CD154 antibody-mediated inhibition[J], J Immumol 2001,167(1):156-162.
    [71]Neumann D etc, IL-12 upregulates the IL-18chain in balb/c thymocytos [J]. J Interferon Cytokine Res,2001,21(8):635-42.
    [72]Muller U. IL12-independent IFN-gamma production by T cells in experimental Chaga disease is mediated byIL-18[J]. J Immunol,2001,167(6):3346-53.
    [73]Rogge L, Barberis-Maino L, Bifi M, et al. Selective expression of an interleukin-12 receptor component by human T helper 1 cells[J]. J Exp med, 1997,185:825-831.
    [74]Padigel UM. The Development of a Thl,TH3e Respork, e and Resistance to Leishmania major Infect ion in the Absence of CD40-CD40L Costimulation [J]. J Immunol,2001,167(10):5874-5879.
    [75]Bullens DM, Kasran A, Thielemmls K, CD40L-induced IL-12 production is further enhanced by the Th2 cytokines IL-4 and IL-13[J] Scand J Inlnlunol,200 L,53(5):455-63.
    [76]Borish L, Rosenwasser LJ. Update on cytokines. [J]Allergy Clin Immanol, 1996,97(3):719-733.
    [77]Foli A Barnea A znogel L Effects of the Th1 and Th2 stumulacory cytokines mterleukin-12 and interleukin-4 on human mumunodeficiency [J].vitus replication Blood.1995; 85:2114-2123.
    [78]Lamont AG, Adocini L IL-12:a key cytokine m mumune regulation [J] Immune Today,1996; 17:214-217.
    [79]Yawalkar N, Karlen S, Egli F, Brand CU, Graber HU, PichlerWJ, et al. Down regulation of 1L-12 by topical corticosteroids inchronic atopic dermatitis[J]. J Allergy Clin hnmunol,2000,106.
    [80]Chehimi J Tnnchieri G Interleukim-12:a bndged between resistance and adaptive enmunity with a role on infection and acquired mumnodeficiency [J].Chen Jmmund.1994,14:149 161.
    [81]NikhnY。 Stephan K, Fabierme E, et al. Down-regulation Of IL-12 by topical corticosteroids in chtonic atopic dermatitis[J]. Allergy Clin Immunol, 2000,105(5):941.
    [82]Mazzeo D. Panina-Bordignon P, Recalde H。 et al. Decreased IL-12 production and Thl cell development acetyl salicylic acid-mediated inhibition of NF-kB. Eur[J].Immunnol,1998,28: 3205.
    [83]Hershey GK. IL-13 receptors and signaling pathways:an evolving web. [J]Alergy ClinImmunol,2003,111:677-690.
    [84]林晓明.白介素13在哮喘发病机制中的作用[J],国际病理科学与临床杂志,2005,25(6):539-542.
    [85]Blackburn MR, Lee CG, Young HW, et al. Adenosine mediates IL-13induced inflammation and remodeling in the lung and interacts inan IL-13adenosine amplification pathway[J], Clin Invest,2003,112(4):332-344.
    [86]Yasunaga S, Yuyama N, Arima K, et al. The negative-feedback regu-lation of the IL-13 signal by the IL-13 receptor alpha2 chain in bron-chial epithelial cells[J]. Cytokine,2003,24(6):293-303.
    [87]Defrance T。 Carayon P, Billian G, et al. Interleukcin-13 ks a B cell stimulating factor[J]. Exp Med,1994,179:135.
    [88]Punnonen J, Aversa G, Cocks GB, etal. Interleukin-13 induces interleukin 4-independentIgG4 and IgE synthesis andCD23 expression by human B cell[J]. Immunology,1993,90:3730.
    [89]Gauchat JF, Schlagenhauf E, Feng NP, et al. A novel4-kb interleukin-13 receptor alpha mRNA expressed in human B, T and endothelial cells encoding an alternatetype 11 interleukin.4/nterleukinl3 receptor Eur [J] Immun e, 1997,27:971.
    [90]Malefyt DR, Figdor GC, Huijbens HR, et al. Effects of IL-13 onphenotype, cytokine production, and cytotoxic function of humanmonocytes. [J]. Immun-ology,1993,151:637.
    [91]Bochner SB, Klun k AD, Sterbinsky AS, et al. IL-13 seleetively induces vascular cell adhesion molecuh-1 expression in human endothelial cell-s. [J]Immunology,1995,154:799.
    [92]Wongpiyabovom J, Suto H, Ushio H。et al. Up-regulation of interleukin-13 receptor alphal on human keratinocytes in the skin of psoriasis and atopic dermatitis [J]. Dermatol Sci,2003,33(1): 31-40.
    [93]Moore MM, Rifas2Shiman SL, Rich2Edwards JW, et al. Perinatalp redictors of atop ic dermatitis occurring in the first sixmonths of life [J]. Pediatrics, 2004,113:468-474.
    [94]Svejgaard E et al. A cta Derm V enered,1985,114(Suppl):72-76.
    [95]Leung DY, Boguniewicz M, Howell MD et al New insights into atopic dermatitis [J].Clin Invest,2004,113:651-657.
    [96]Novak N, Bieber T, LeungDY. Immune mechanisms leading to atopic dermatitis [J] Allergy Clin Immunol,2003,112 (6):128-S139.
    [97]Lee YA, Wahn U, Kehrt R, et al. A major suscep tibility locus for atopic dermatitis map s to chromosome 3q21.Nat Genet,2000,26:470-473.
    [98]Beyer K, Nickel R, Freidhoff L, et al. Association and linkage ofatopic dermatitis with chromosome 13q12-14 and 5q31-33 markers. [J]Invest Dermatol, 2000,115:906-908.
    [99]BradleyM, Soderhall C, Luthman H, et al. Suscep tibility loci foratop ic dermatitis on chromosomes 3,13,15,17 and 18 in a Swedishpopulation[J]. Hum Mol Genet,2002,11:1539-1548.
    [100]Tsunemi Y, Saeki H, Nakamura K, etal. Interleukin-13 genepoly morphism G4257A is associated with atopic dermatitis in Japanese patients [J]. Dermatol Sci,2002,30:100-107.
    [101]He JQ, Chan Yeung M, ecker AB, et al. Genetic variants of theIL13 and IL-4 genes and atopic diseases in at 2 risk children [J]. Genes Immun, 2003,4:385-389.
    [102]Baker BS. The role of microorganisms in atopic dermatitis[J]. Clin ExpImmunol,2006,144(1):1-9.
    [103]ABECK D, Staphylococcus aureus coloniza-tion in atopic dermatitis and its therapeutic implications [J] Br J Dermatol,1998:139:13.
    [104]MATSUNAGAT, YOKOZAKIH, etal. Superantigen-inducedcytokine expression in organ-cultured human skin [J].J Dermatol Sci,1996,11:104-110.
    [105]Vickery BP. Skin barrier function in atopic dermatitis [J].Curr Opin Pediatr,2007,19(1):89-93.
    [106]陈可冀、姚新生、李恩、危北海、陈士奎等.著名专家学者论中西医结合[J],中医药学刊,2002,20(5):551.
    [107]倪文琼,丁巍,于江亭等.三组药物治疗异住性皮炎前后血清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.
    [108]尤立平.特应性皮炎煎剂疗效及对血清总IgE和EOS的影响[J].中医药学刊,2003:21(6):929—930.
    [109]华海燕,朱金土,余土根.皮炎消净饮Ⅰ号对湿热型特应性皮炎Thl/Th2细胞因子的调控作用[J],中国中西医结合皮肤性病学杂志,2007,6(4):219-221.
    [110]张玉环,陈保疆.中西医结合治疗特应性皮炎的临床研究[J].中国中西医结合皮肤性病学杂志,2005,4(4):207-210.
    [111]尤立平,刘永生.复方甘草酸苷治疗特应性皮炎临床疗效观察[J].中华实用中西医杂志,2005,8(18):1138-1139.
    [112]邹移海,徐志伟.实验动物学[J].科学出版社.2004.1.
    [113]朱金土,余土根,杨锋等.皮炎消净饮1号冲剂治疗异位性皮炎的实验研究[J].中国现代应用药学杂志,2001,18(6):411.
    [114]沉小珩,朱伟嵘.地参祛风合剂抗过敏反应的实验研究[J].中国中医药科技,2007,14(5):318-319.
    [115]王琼,张莉敏.除湿糊剂治疗特应性皮炎的实验与临床观察[J].吉林医学,2006,27(11):1399-1400.
    [116]李忻红,田静.补肾养血煎剂治疗儿童特应性皮炎的实验研究[J].中国中医药科技,2005,12(3):150-151.
    [117]刁庆春,薛梅,唐海燕.祛风利湿法对特应性皮炎Thl/Th2细胞调节的实验研究[J].四川中医,2007,25(8):16-18.
    [118]刘源,叶秋华,陈加媛.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.
    [119]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):83
    [120]孙小冬,中药健脾渗湿冲剂治疗特应性皮炎的疗效及其复发影响的评价[J].人民卫生出版社,2008,1:264-274.
    [121]沉小珩.祛风合剂对Ⅰ型变态反应影响的实验研究[J].上海中医药杂志,2001,12(12):39.
    [122]宫本朋美.苦参中的止痒成分[J].国外医学中医中药分册,2004,26(3):186.
    [123]王欣,孟丽华.特应性皮炎中医治疗进展与展望[J].中医药临床杂志,2005,17(3):309-311.
    [124]丰哲,刘华盛,黄有荣.中西医结合是系统论于还原论统一的最佳形式[J].世界中西医结合杂志,2008,3(1):50—52.
    [125]朱立宏.徐宜厚从心脾论治小儿皮肤病的经验[J].湖北中医杂志,2001;29(4):10-11.
    [126]Williams HC, Pembroke AC. Inforaorbital crease, ethnic group, and atopic dermatitis[J]. Arch Dermatol,1996; 132(1):51-54.
    [127]刘炽.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[D].广州中医药大学博士学位论文.2009,4.
    [128]曾迎红,赵蕊,叶志纯.儿童异位性皮炎血清IL-4,IL-5及IgE水平的测定[J].中国当代儿科杂志,2004,6(5):407-408.
    [129]Kimata H. Selective ancement of production of IgE. IgG4. and Th2 cell cytokine during the rebound phenomenon in atopic dermatitis and preventionby suplatast tosilate[J]. Ann Allergy Asthma Immunol,1999,82(3):293-295.
    [130]Rajka G Langeland T Grading of the severity of atopic dermalitis Acta Den Venereol Suppl Stockh[J],1989,144:13-14.
    [131]Kimura M. Tsunta S Yoshida Correlationof house dust mite specific lymphocyte profifemtionwith IL-5 production, eosinophiliaand the severity of symptoms in infants withatopie dermatitis[J]Al Lergy Clin Immunol,1998,101: 84-89.
    [132]刘宝军等.特应性皮炎患者血清白介素5水平测定[J],中华皮肤科杂志,2001,34(6):446.
    [133]曾迎红等.儿童异位性皮炎血清IL-4,IL-5及IgE水平的测定[J].中国当代儿科杂志,2004,6(5):407-408.
    [134]范团起等,异位性皮炎血清IL-10及IL-12水平检测及临床意义[J].医药论坛杂志,2006,27(11):4-6.
    [135]熊芬等,特应性皮炎患者血清白介素-18及12水平检测及临床意义[J],临床皮肤科杂志,2005,34(6):364-365.
    [136]Wang LF, Wu J, Sun CC, et al. Local but not systemic administration of IFN-gamma during the sensitization phase of protein antigen immunization suppress Th2 development in a murine model of atopic dermatitis [J]. Cytokine, 2002,19(3):147-152.
    [137]Takahashi N, Akahoshi M, Matsuda A. et al. Association ofIL-12R[31 promotor polymorphisms with increased risk ofatopic dermatitis and other allergic phenotypes[J]. Hum MolGenet,2005,13:327.
    [138]Aktas E, Akdis M, Bilgic S, et al. Different natural killer receptor expression and immunoglobulin E regulationbNKl and NK2 cells[J]. Clin Exp Immunol,2005,140(2):301-309.
    [139]Liu M, Zheng S, Wang X, et al. Regulatory roles of IL-12. IL-4 and IFN-gamma on IgE synthesis in atopic patients[J]. Cli Med J,1999,12(6):550-553.
    [140]Habu Y, Seki S, Takayama E, et al. The mechanism of a defective IFN-gamma response to bacterial toxins in an atopic dermatitis model, NC/Nga mice, and the therapeutic efect of IFN-gamma, IL-12, or IL-18 on dermatitis [J]. Immunol,2001,166(9):5439-5; 447.
    [141]Teraki Y, Hotta T, Shiohara T. Increased circulating skin-homing cutaneous lymphoeyte-associated antigen(CLA)+ type 2 cytokine-producing cells, and decreased CLA+ type 1 cytokine-producing cells in atopic dermatitis[J]. Br J Dennatol,2000,143(2):373-378.
    [142]李建民,特应性皮炎患者IL-13.IgE水平的检测及临床意义[J].右江民族医学院学报,2005,27(1):60.
    [143]单如梅,张海燕,张娟华.变态反应疾病诊断与检测血清中过敏原及总IgE的关系[J].临床杂志,2002,3(2):86.
    [144]Purmonen J AceroaG. Cc ksGB, et. Iater lenkitt-13 inducesinter-lenkin 4-iadepedettt I and IgE synthesis and CD23 exprexskm by human B cell [J]. Immundogy,1993,90:3730.
    [145]李建民,特应性皮炎患者IL-13、IgE水平的检测及临床意义[J].右江民族医学院学报,2005,27(1):60.
    [146]陈达灿,吴晓霞.特应性皮炎中西医结合治疗[M].北京:人民卫生出版社,2008:222-255.
    [147]陈达灿,榻国维.皮肤性病科专病[M].北京:人民卫生出版社,2000:116-117.
    [148]Shi L, Meng Y W, Li W. Progress of Potygonatum and itspolysaccharides studies on pharmacology [J]. Nat Prod Res Dev(天然产物研究与开发),1999,11:67-71.
    [149]宋海英,邱世翠,王志强.金银花的体外抑菌作用研究[J].时珍国医国药,2003,14(5):269.
    [150]郝书江.甘草应用浅淡[J].时珍国药研究,1997,8(1):94.