银屑灵片处方优化的实验研究及临床探索性研究
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
     银屑病是一种常见的皮肤病,是多基因遗传背景和环境等多因素作用下T细胞介导的免疫异常性疾病,其发病机制仍不清楚。当前不管是内用药还是外用治疗都不能完全根治银屑病,自然缓解病例非常少,在需长期甚至终生治疗的情况下,选择有效而副作用少又经济的治疗方案成为客观的需要。在我国,长期的临床实践证明:中药治疗银屑病毒副作用少,疗效持久,提高患者的生存质量。研究中药治疗银屑病具有广阔的应用前景。
     目的
     对银屑灵片处方进行配伍筛选,寻找最佳处方组成。探讨银屑病中医证型与病情严重程度及疾病分期的相关性,了解银屑病中医证型在人群中的分布,对银屑灵片优化方的应用提供参考。并将银屑灵片优化方运用于临床,对其治疗寻常型银屑病的临床疗效及初步安全性进行探索性分析。
     方法
     1实验研究:
     1.1银屑病不同环节或表现的病理模型的建立,包括瘙痒模型,小鼠鼠尾颗粒层形成模型,以观察银屑灵片对瘙痒模型和鼠尾鳞片颗粒层形成模型的影响。
     1.2对处方中药物,采用正交设计的方法,选择L12(211)正交实验表安排实验,进行组方配伍的初步筛选。
     1.3对银屑灵片原方、银屑灵片优化方和作用显著方再次进行药效学实验,验证正交实验结果的可靠性。
     2临床流行病学调查:
     采用横断面调查的临床研究方法,对280例符合诊断及纳入标准的寻常型银屑病人进行问卷调查。问卷及调查表由三部分组成,第一部分为患者的基本情况。第二部分为医生评价指标,包括银屑病皮损面积与严重程度指数(PASI评分)。第三部分为患者自评,包括VAS (visual analog scale)评分和患者或家属对疾病目前状态的总评、心理状态自评包括SDS量表和SAS量表。统计学方法包括秩和检验、卡方检验、方差分析以及非条件逐步多元Logistic回归分析、相关分析。
     3临床探索性试验:
     采用描述性研究的临床试验性研究方法,即Ⅳ型设计方案。纳入22例合格受试者,服用“银屑灵片优化方”,进行为期2个月的临床观察,服药后1个月、服药后2个月作为观察时点,记录PASI评分、DLQI评分及不良事件观察表等,以期初步观察“银屑灵片优化方”的临床疗效及初步安全性。
     结果
     3.1实验研究:
     3.1.1银屑灵片低、中、高剂量组对右旋糖酐诱导释放内源性组胺动物瘙痒模型具有较好的止痒作用,其中银屑灵片中、高剂量与扑尔敏作用相当。银屑灵片高剂量组对外源性组胺的释放有较好的对抗作用,其与扑尔敏作用相当。银屑灵片高剂量组在止痒方面的作用明显优于迪银片。
     3.1.2银屑灵片各剂量组对小鼠尾鳞片颗粒层的形成均有明显的促进作用,其中银屑灵片高、中高剂量组的作用明显优于迪银片,而中、中高、高剂量组的作用与甲氨蝶呤组的作用相当。银屑灵片中、中高、高剂量组作用优于低剂量组,但各组间作用相当。
     3.1.3根据正交拆方后实验结果,银屑灵片拆方中止痒的最优组合为乌梅、甘草、紫草、金粟兰、土茯苓。促进小鼠鼠尾鳞片表皮颗粒层形成的最优组合是赤芍、土茯苓、莪术。综合两组实验结果,确立银屑灵片优化方处方组成为:赤芍、莪术、乌梅、紫草、金粟兰、土茯苓、甘草。
     3.1.4以瘙痒模型比较银屑灵片原方、银屑灵片优化方与拆方后药效最优方之间的药效学差异,观察结果提示,与空白对照组相比,银屑灵片原方、银屑灵片优化方、拆方后药效最优方组均与之差异有统计学意义(P<0.05)。银屑灵片原方、银屑灵片优化方与拆方后药效最优方各组间比较差异无统计学意义(P>0.05)。结果提示,银屑灵片原方与银屑灵片优化方对小鼠瘙痒模型的止痒作用相当,说明正交结果可靠。
     3.2临床流行病学调查
     3.2.1 (1)寻常型银屑病患者中医证型与疾病分期的分布规律:本次调查显示,寻常型银屑病的中医辨证分型中,以血瘀证最为常见,占69%;疾病分期中以稳定期最为常见,占58%。据本次调查结果推测在寻常型银屑病的人群分布中,血瘀证与稳定期的病人所占比例最高。
     (2)中医证型与疾病严重程度关系探讨:通过分析不同中医证型间各项病情评判指标的差异,可得三种证型的PASI评分存在明显的差异,其中风热证的PASI评分最高,血瘀证次之,血燥证最低。且除头部外,与上肢、躯干、下肢的PASI评分严重度对应。因此,可以推测风热证的患者病情较重,血瘀证次之,血燥证最低。通过三种证型影响因素的非条件逐步Logistic回归分析,可以看出PASI躯干评分与VAS评分越高的患者,患者为血瘀证的可能性越小;PASI躯干评分与VAS评分越高,患者为风热证的可能性越大,但由于这两个变量的OR值接近1,提示这两个变量为风热证的低度相关因素;PASI躯干评分与VAS评分越高,得血燥证的可能性越大,年龄分段的值越高患者为血燥证的可能性越小。
     (3)中医证型与银屑病分期的关系:证型与银屑病分期的对应分析显示:风热证与进行期相关,血瘀证与稳定期相关,消退期与血燥证相关。
     3.3临床探索性试验
     3.3.1依从性分析:22例受试者中21例患者完成试验,根据面询法及患者用药日记统计结果,95%患者依从性好。
     3.3.2疗效分析:
     (1)22例受试对象疗前与疗后1个月、2个月的PASI评分,差异均有统计学意义(P<0.01和P=0.05)。治疗后1个月,14%的受试对象达到了PASI-75,43%的受试者达到PASI-50,PASI评分与治疗前相比平均改善了28%;治疗2月后,10%的受试对象达到了PASI-75,30%的受试对象达到了PASI-50, PASI评分与疗前相比平均改善12%。
     (2)治疗后1月与治疗后2月DLQI评分改善率分析可见,治疗1月后,受试对象的生活质量评分改善平均改善了10%,改善最显著的受试对象达73%;治疗2个月后,受试对象的生活质量评分平均改善了12%,改善最显著为89%。
     (3)三种证型治疗后2个月的DLQI评分差异有统计学意义(P<0.05),风热证的评分最高,血瘀证次之,血燥证最低,提示风热证患者的生活质量相对最差,血燥证患者的生活质量相对较好。
     3.3.3初步安全性分析:本次试验全部观察病例未有出现恶心呕吐、腹痛腹泻者,无不良事件发生。初步显示安全性好。
     结论
     4.1实验研究:银屑灵片具有止痒及促进小鼠鼠尾鳞片表皮颗粒层形成的作用,以此为病理模型筛选出的“银屑灵片优化方”药简而力宏,具有进一步深入研究的潜力和价值。
     4.2临床流行病学调查:据本次调查结果显示,血瘀证与稳定期的病人在本次研究中所占比例最高。不同中医证型间银屑病的疾病严重程度可能存在差异。证型与银屑病分期可能有对应关系,对应分析显示:风热证与进行期相关,血瘀证与稳定期相关,消退期与血燥证相关。
     4.3银屑灵片优化方经实验验证并运用于临床探索性试验,初步显示本处方安全有效,值得深入研究。
Background
     Psoriasis is a common, genetic, inflammatory, multisystem, T-cell interaction disease with pathognesis has not been completely defined. Nowadays without any drug can cure Psoriasis completely. It is objectivity neeed to find some safey drugs witch may confer less rik and side sffects. Traditional Chinese Medicine (TCM) with longterm effectiveness, but less side sffects and toxicity,can improve patient's quality of life. TCM has widely application prospect.
     Objective
     To find the best formulation composition of Yinxieling Capsule. Research into the relevance of syndrome type of TCM with sverity and stag of psoriasis. Understand the distribution of syndrome type of TCM in the population, in order to offer reference of using the optimize of Yinxieling Capsule.Evaluate the safety and efficacy of the optimize of Yinxieling Capsule.
     Methods
     1. Experimental research:Establish different segments or pathology model, such as itching animal model and mouse tail model for doing optimization operations. To made model of pruritus by the method of inducing endogenous histamine releasing in the using of dextran-40, To observe the time (latent time) of the first time scratching after giving dextran-40 in Jimpy mice and frequency of scratching in 30min. To give histamine phosphate by endermic injection at the same time giving yiwensi physiologic saline to dye skin of Jimpy mice' hypogastric zone, to cut blue-stain skin and to survey areas. Used a mouse tail model, to counter the number of scales which contained the granular cell in lines consecutively 100 scales. Arrange experiments with the orthogonal design. Tweleve experiments were carried out by L12 (211) orthogonal design. Screening the best optimization named The Optimization of YinXieLing Capsule. Then verification its effect with YinXieLing Capsule.
     2. The clinical epidemiological investigation:TO study the 280 psoriasis vulgaris patients'questionnaires with cross-section survey method. The questionnaires make up with 3 parts:common conitions, pysician-assessed outcomes and patient-reported outcomes. SPSS13.0 for windows Chi-square test, Rank sum test, ANOVA test and multiple logistic regression analysis, Bivariate Correlations were used in this research.
     3. Clinical scoutingtest:A descriptive research study design was used in this study.22 patients with psoriasis vulgaris were bring into this study. The observation has been lasting 2 months. Record PASI DLQI and adverse event every month after The Optimization of YinXieLing Capsule treatment.
     Results
     1. Experimental research:
     1.1 Latent time of yinxieling Capsule group in low、middle or high dose are obviously longer than blank group, but frequency of scratching obviously decrease (p<0.01) among the total, There are not obviously difference among yinxielingpian group in middle or high dose and chlorphenamine group, wheal area of dyeing skin of Jimpy mice'hypogastric zone in high group obviously decrease than blank group(p<0.05), but not obviously difference between high dose and chlorphenamine group. Latent time、frequency of scratching and wheal area all outstrip yindipian.
     1.2 There were highly statistically significant compared each dosage of YinXieLing Capsule with negative control group(P<0.01). Compared the Methotrexate group, no statistically significant difference was found with the highest, higher and medium dosage groups. Also the Diyin film group compared with medium and lower dosage groups (P>0.05). Even more scales were found by the highest, higher and medium dosage groups than Diyin Capsule group (P<0.01). And compared with each dosage of YinXieLing Capsule, the highest, higher and medium dosage groups were highly statistically significant with the lower dosage group(P<0.01). But no statistically significant difference in themselves(P>0.05).
     1.3 The Optimization of YinXieLing Capsule is made into Raix Paeoniae Rubra、Fructus Mume、Rhizoma Curcumae、Glabrous Greenbrier Rhizome、Radix Paeoniae Rubra、Chloranthus spicatus (Thunb.) Makino, Radix Glycyrrhiza.
     1.4 There were highly statistically significant compared YinXieLing Capsule and The Optimization one with negative control group(P<0.01). Compared YinXieLing Capsule group, no statistically significant difference was found with The Optimization one(P>0.05).
     2. The clinical epidemiological investigation:Laws of poriasis vulgaris patients with diseases card type of traditional Chinese medicine in the distribution of the results of this survey:blood stasis syndrome and the stationary phase of psoriasis vulgaris is the most common, with 69% and 58%. different syndrome types of traditional Chinese medicine(TCM) has different outcomes. Correspondence analysis has been taking into Syndrome types of TCM and the phase of psoriasis vulgaris. blood stasis syndrome has relationship with the stationary phase. Wind-heat with development phase, and blood-dryness with fade phase.
     3. Clinical scoutingtest:
     3.1 Intention to treat analysis:22 patients finish the test, according to the enquiry and the patients'getting records,95% of the statistics Intention to treat analysis well.
     3.2 Treatment Efficacy:14% of the patients achived PASI-75 after one month treatment, and PASI-50 is 43%,28% average improved.10% of the patients achived PASI-75 after one month treatment, and PASI-50 is 30%,12% average improved. There were highly statistically significant compared after 1 month and 2 months treatment with before (P≤0.05). After I month treatment 10% improved in DLQI and 12% after 2 months.
     3.3 Safety Evaluation:The experiment has not been observed in all cases of sickness, diarrhea and vomiting have no adverse events, preliminary showed good Safety.
     Conclusion
     Yinxieling Capsule have better alleviating itching effect. The formation of granular cell of mouse tail was significantly promoted by each dosage group of YinXieLing Capsule. The Optimization of YinXieLing Capsule has less drug but same effects.
     According to The clinical epidemiological investigation:Blood stasis syndrome and the stationary phase of psoriasis vulgaris is the most common, with 69% and 58%. different syndrome types of TCM has different outcomes. Correspondence analysis has been taking into Syndrome types of TCM and the phase of psoriasis vulgaris. blood stasis syndrome has relationship with the stationary phase. Wind-heat with development phase, and blood-dryness with fade phase.
     In this 2 months study the Optimization of YinXieLing Capsule reulted in significant improvements in clinical end points in patients with this study.
引文
[1]邵长庚.我国银屑病的流行和防治现状[J].中华皮肤科杂志,1996,29(2):75-76.
    [2]徐元勇,叶冬青.安徽省宿州地区农村居民四种皮肤病流行病学调查[J]中华皮肤科杂志.2002,35(5):406-407.
    [3]Raychaudhuri SP, Farber EM. The prevalence of psoriasis in the world. J Eur Acad Dermatol Venereol,2001,15(1):16-17.
    [4]靳士英,靳朴.《五十二病方》“疕”病考[J].中华医史杂志.1997,27(3):165-166.
    [5]榻国维,范瑞强,陈达灿.中医皮肤病临证精粹[M].广东:广东人民出版社,2001:113.
    [6]刘凤年.卢传坚教授治疗银屑病经验介绍[J].新中医,2006,38(6):13.
    [7]李静.徐丽敏教授从血辨治银屑病经验介绍[J].新中医,2007,39(12):10.
    [8]赵炳南,张志礼.简明中医皮肤病学[M].北京:中国展望出版社,1983:200-203.
    [9]秦万章.银屑病血证与调血研究[J].中国中西医结合皮肤性病学杂志.2007,7(1):1-4.
    [10]宋坪,李博鉴.从血论治、诸法合用,朱仁康研究员治疗银屑病经验[J].中国中西医结合皮肤性病学杂志,2004,3:1-2.
    [11]金起凤,周德英.中华皮肤病学[M].北京:中国医药科技出版社,2001,228-233.
    [12]刘卫红,李萍,王萍等.银屑病血热证患者治疗前后血浆代谢组学分析[J].首都医科大学学报.2009,30(4):430-435.
    [13]彭振辉,张美芳,张秉正,等.银屑病中医分型血清TGF-β、TNF-α的生物测定[J].中国皮肤性病学杂志.2000,14(1):2-3.
    [14]程滨珠.银屑病患者血清肿瘤坏死因子水平与中医证型关系的初步研究[J].中国中医基础医学杂志.1999,5(9):42-43.
    [15]程滨珠.银屑病患者有关细胞因子水平与中医辨证分型的相关性研究[J].中国中医药科技,1999,6(5):286.
    [16]王萍,张梵,李伟凡,等.凉血活血汤治疗寻常型银屑病临床观察及TNF-a水平检测[J].中国皮肤性病学杂志,2001,15(2):90-91.
    [17]单筠筠,宋秀祖,尉晓冬,等,银屑Ⅰ号治疗寻常性银屑病临床疗效观察及相关细胞因子检测[J].中国中西医结合皮肤性病学杂志,2006,5(2):87-88.
    [18]陈红,王思平.复方青黛胶囊治疗寻常型银屑病的疗效观察及其对血清IL-2、IL-8的影响[J].中药材,2004,27(11):885-886.
    [19]姜一化,郑义,高进,等.祛银汤体外对银屑病抗体依赖细胞介导生长刺激模型 影响的研究[J].中国实验方剂学杂志,2001,7(6):45-47.
    [20]于延,刘晓明,侯素春.凉血活血复方治疗寻常型银屑病及对血清IL-8的影响[J].中国麻风皮肤病杂志,2005:21(9):712-714.
    [21]娄卫海,张志礼,邓丙戌,等.凉血活血汤治疗进行期银屑病的临床及实验研究[J].中华皮肤科杂志,1999,32(2):.80-81.
    [22]于延,刘晓明,侯素春.凉血活血复方治疗寻常型银屑病及对血清IL-8的影响[J].中国麻风皮肤病杂志,2005,21(9):712-714.
    [23]张云璧,瞿幸,牛福玲.常用治疗银屑病的中药对肿瘤坏死因子-α刺激后角质形成细胞生长及分泌白介素-8的影响[J].中国中西医结合皮肤性病学杂志,2006,5(1):18-20.
    [24]张颖.中医辨证分型治疗银屑病280例[J].云南中医中药杂志,2008,29(3)15-16.
    [25]钟金宝,李仰琪,梁燕梅.中医辨证治疗寻常型银屑病96例[J].江西中医药,2007,8(38):33-34.
    [26]李丽琼,欧阳晓勇.刘复兴治疗银屑病经验[J].云南中医中药杂志,2003,24(1):2-3.
    [27]李咏梅,马绍尧,冯国强等.论治银屑病495例疗效观察[J].江中西医结合杂志.2007,17(12):776.
    [28]侯明.凉血解毒汤治疗银屑病临床疗效观察[J].辽宁中医杂志,2008,35(3):408-409.
    [29]孙元亮.活血化瘀法治疗寻常型银屑病125例[J].湖南中医杂志,2007,23(5):58.
    [30]陈艳,历志,刘立红.美能合并黄连解毒汤加味治疗银屑病28例疗效观察[J].哈尔滨医药,2007,27(6):42-43.
    [31]刘环清.凉膈散加减治疗寻常型银屑病的临床观察[J].中国中医药科技,2007,14(4):234.
    [32]单敏洁.清瘟败毒饮治疗急性重症皮肤病举隅[J].新中医,2007,39(12):70-71.
    [33]雷三礼,刘发利.青黛藓皮汤治疗银屑病54例临床观察[J].实用医技杂志,2007,14(18):2474-2475.
    [34]陈跃东.清热凉血汤治疗寻常型银屑病78例[J].黑龙江中医药,2008(1):18-19.
    [35]林茂,熊芬,侯秀芹等.乌梅合剂治疗寻常性银屑病临床观察[J].医学信息,2008,21(1):111-112.
    [36]李彦恒,李园春,陈洪文.乌牛汤治疗银屑病286例[J].医学理论与实践,2008,21(3) : 313.
    [37]李洪玲,于杰.消银汤治疗寻常型银屑病96例临床观察[J].中国中医药科技, 2007,14(6):473.
    [38]荆夏敏,胡梁谱,彭继斌等.宣肺扶阳汤治疗关节型银屑病35例[J].实用中医药杂志2008,24(2):93.
    [39]黄国林.消银方治疗寻常型银屑病50例[J].湖南中医杂志,2002,18(6):45.
    [40]毕艳武.自拟凉血解毒消斑汤治疗寻常型银屑病60例[J].实用中医内科杂志,2007,21(10):37.
    [41]刘永富,刘俊峰.消银汤联合雷公藤多甙片治疗寻常型银屑病临床观察[J].中国麻风皮肤病杂志,2007,23(10):927-928.
    [42]华玫,戴志军.丹苓抗银胶囊治疗寻常型银屑病临床观察[J].中华临床医学杂志,2007,8(6):57-58.
    [43]王荫范,田秋真,李兆辉等.银屑平丸治疗银屑病的临床研究[J].河北中医,2006,28(7):498.
    [44]白彦萍,杨项权,王煜明等.祛银颗粒治疗血热型银屑病疗效分析[J].中国麻风皮肤病杂志,2007,23(12):1065-1067.
    [45]王远红,张敏娜,匡海学等.扫癣灵治疗寻常型银屑病46例临床观察[J].中国中医药科技,2006,13(6):379.
    [46]高学文,于洁,李丹.消银Ⅰ号胶囊的制备及临床应用[J].中国现代医生,2007,45(22) : 82,84.
    [47]詹庆霞,徐丽敏.雷公藤治疗银屑病的系统评价[J].中国中西医结合皮肤性病学杂志,2007,6(3):192-193.
    [48]靳隽.雷公藤多甙和阿奇霉素治疗寻常型银屑病65例[J].医药论坛杂志,2007,28(14): 60,62.
    [49]杜冠华,张均田.丹参现代研究及进展[J].医药导报2004,23(7),435—438.
    [50]赵红,张华,沈玉静.丹参酮胶囊在皮肤科的应用[J].医学综述,2007,13(24):2048-2049.
    [51]王水电,张子琦.复方丹参静滴治疗银屑病32例[J].现代中西医结合杂志20035,12(3):245.
    [52]蒋昕,黄俊华.复方丹参注射液治疗扁桃腺炎并发银屑病32例疗效观察[J].医学信息,2008,21(1):108-109.
    [53]吴卫.鱼腥草的研究进展[J].中草药,2001.32(4):367-368.
    [54]王鹏,迪丽努尔,高瑾等.鱼腥草治疗寻常性银屑病疗效对比及远期随访观察[J].中国皮肤性病学杂志,2007,21(7):445.
    [55]周淑维,宋坪,刘瓦利等.清开灵注射液治疗银屑病血热证观察[J].中国中医基础医学杂志,2003,9(11):37,39.
    [56]刘涛,杜宇,陈德宇.补骨脂注射液联合冰黄肤乐软膏治疗寻常型银屑病疗效观 察[J].岭南皮肤性病科杂志,2008,15(1):25-26.
    [57]南淑华,红皮病型银屑病淀粉药浴的护理[J].中国皮肤性病学杂志,2007,21(9):566.
    [58]夏晓君.青连软膏治疗寻常型银屑病疗效观察[J].山东中医杂志,2008,27(2):99-100.
    [59]贾丽梅,王学军.消屑灵软膏治疗寻常型银屑病(血虚风燥型)192例疗效观察[J].黑龙江中医药,2007(4):13-14.
    [60]杨岚.中药浴治疗寻常型银屑病30例临床观察[J].北京中医,2007,26(11):733.
    [61]邹学敏.中药熏蒸配合PUVA治疗寻常型银屑病的疗效观察与护理[J].中医外治杂志,2007,16(6):28.
    [62]张淑萍.矿泉浴并紫外线(UrN)治疗寻常型银屑病疗效观察[J].中国疗养医学,2008,17(3):135.
    [63]赵玉珍,赵广.矿泉浴联合窄谱中波紫外线照射治疗寻常性银屑病45例疗效观察[J].临床皮肤科杂志,2008,37(3):196-197.
    [64]淑萍.矿泉浴并紫外线(UrN)治疗寻常型银屑病疗效观察[J].中国疗养医学,2008,17(3):135.
    [65]毛小爱.埋线配合自血疗法治疗寻常型银屑病38例[J].上海针灸杂志,2007,26(12) : 29.
    [66张学玲,毛东军,沈景刚.银屑病患者心理健康水平的评估及心理治疗[J].中国麻风皮肤病杂志,2007,23(12):1117.
    [67]路云环,李桂霞,范慧英.心理治疗对银屑病患者的影响[J].中国麻风皮肤病杂志,2007,23(1):969-971.
    [68]曾敏帆,刘藕根,姜美英等.辅助心理康复治疗银屑病及其对患者SDS和SAS水平的影响[J].实用临床医学,2007,8(7):25-26.
    [69]王喜国,陶刚,罗平.心理干预与药物联合治疗寻常型银屑病[J].中华临床医学杂志,2008,9(2):84-85.
    [70]攸俊琪.心理干预对银屑病病人病情转归的影响[J].护理研究,2007,21(8):2220-2221.
    [71]景新美国银屑病治疗药市场到2016年可超过90亿美元[J]国外医讯,2007(5):47-48
    [72]陈奇.中药药效研究思路与方法.人民卫生出版社[M],2005.第1版.1067
    [73]孙艳.养血止痒胶囊对小鼠瘙痒模型的实验研究[J].齐齐哈尔医学院学报,2005,26(1): 19-20
    [74]丁媛.瘙痒的发生机制、相关疾病和治疗.中国麻风皮肤病杂志,2006,22(6):493.
    [75]Ramsay B,O'reagan M. A survey of the social and psychological effects of psoriasis. Dr Dermatol,1998,36:195-201.
    [76]张开红,李洪亮.银屑病患者生活质量调查与分析[J].中国行为医学科学,2001,10(6):558-561.
    [77]王万卷,苏宝山,谭升顺.P物质和表皮生长因子受体在早期银屑病发病中的作用[J].西安交通大学学报(医学版),2004,25(2):131.
    [78]齐宝全,陆洁,段听所.银屑病皮损处角质形成细胞中P物质的研究.临床皮肤科杂志,2004,33(7期):415.
    [79]吕世超,关鹏举,王萍.银屑病患者皮损P物质含量的检测[J].中华皮肤科杂志,1998,31(2):102.
    [80]杨慧敏,徐佳,杨岚.皮肤瘙痒的发生机理与中医辨证施治相关性探讨[J].中国中西医结合皮肤性病学杂志,2006,5(3):175、178、180.
    [81]Jarrett A. The physiology and pathophysiology of the skin[J]. London Academic Press,1973,1:123.
    [82]Speaman RIC, Jarrett A. Biological comparison of isomers and chemical forms of vitamin A[J].Br J Dermatlog,1974,90:553.
    [83]Jongh. Gys. J, Zeeuwen. Patrick L. J. M., Kucharekova. Martina, et al.High Expression Levels of Keratinocyte Antimicrobial Proteins in Psoriasis Compared with Atopic Dermatitis[J]. Journal of Investigative Dermatology, 2005,125 (6),1163-1173.
    [84]赵小东,付荫,卢涛等,银屑病成纤维细胞培育上清对角质形成细胞增殖的影响[J].中华现代皮肤科学杂志,2004,1(2),103-105.
    [85]高奎斌,李萍,王雅坤等,寻常型银屑病患者皮损中Caspase-3和bcl-xL的表达[J].中华皮肤科杂志,2004,37(10),587-588.
    [86]齐宝全,陆洁,段昕所等,银屑病皮损处角质形成细胞中P物质的研究[J].临床皮肤科杂志,2004,33(7),415-416.
    [87]孙令,高明阳.鼠尾鳞片不全角化表皮的凝集素标记观察[J].大连医学院学报,1992,14(1):23.
    [88]丁薇,马丽俐.银屑病免疫学发病机制及相关转基因动物模型研究进展[J],中国中西医结合皮肤性病学杂志,2009,8(3):190-193.
    [89]高春芳,郑茂荣。银屑病转基因动物模型研究进展[J],国外医学皮肤性病学分册,2000,26(6):343-345.
    [90]王香兰,张秉正,王俊民,等.银屑病中医分型的血流变学及超微结构相关性研 究[J].中国皮肤性病学杂志,2001,15(3):146-148.
    [91]杜桂芹,常曼丽,王秀云.银屑病患者检测血小板指数及血流变的临床意义[J],中国微循环,2004,8(3):180-181.
    [92]刘国海,张贵田,刘庆明等.活血逐瘀汤治疗银屑病及对血流变学的影响[J],陕西中医,2009,5:540-541.

© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号

地址:北京市海淀区学院路29号 邮编:100083

电话:办公室:(+86 10)66554848;文献借阅、咨询服务、科技查新:66554700