【作者】 刘俊峰；

【导师】 陈达灿；

【作者基本信息】 广州中医药大学 ， 中西医结合临床， 2010， 博士

【摘要】 研究背景特应性皮炎(atopic dermatitis, AD)是一种慢性、复发性、瘙痒性皮肤病,严重影响着患者的身体、心理、行为等多方面的健康。近年来AD发病率呈逐年上升趋势,因其发病机制尚不明确,西医治疗只能在一定程度缓解症状,对于顽固病例则不能取得满意疗效。中医药作为一种有效治疗方法,不仅能够缓解症状,而且能够改善患者生活质量,被越来越多的用于治疗特应性皮炎的临床和实验研究,因此关于本病的中医治疗已成为研究的热点。目前国外对中医中药的研究比较深入,研究人员发现单味中药或者有限的几味中药提取物组成的复方确有疗效,尤其在抗炎及免疫调节方面的作用得到了肯定。国内中医药治疗AD多为辨证论治、经验方研究,其具体作用机理尚待阐明。培土清心法是导师陈达灿教授多年临床实践中的经验总结,具有较好的临床疗效。近年来关于AD的发病机理在免疫方面研究有了较大进展,与此同时也发现营养代谢因素在AD的发病过程中也有着重要的作用,中医药治疗疾病是多靶点的,本研究通过检测AD患者治疗前后的n-6脂肪酸水平的变化,探讨培土清心方治疗特应性皮炎可能的作用机理；AD作为一种心身疾病,剧烈的瘙痒、睡眠紊乱以及病情的反复给患者心身造成了巨大的压力,行为学的异常是疾病困扰患者的一种外在表现,也是影响患者生活质量很重要的一方面,目前逐步引起人们的重视,本研究也通过治疗前后患者行为学的变化以探讨中药培土清心方对AD行为的影响。临床研究目的了解特应性皮炎儿童患者行为情况,观察培土清心方治疗特应性皮炎的临床疗效及治疗后患者行为的变化。方法临床疗效观察：本研究选择6—11岁AD患者为研究对象,用中药培土清心方内服,辅以润肤剂外用治疗,以SCORAD积分进行评价,治疗前及治疗后3个月分别记录SCORAD积分及主观症状的变化。对行为学的影响：所有患者治疗前及治疗后由父母填写Conners父母用症状问卷,并与中国城市常模进行比较,并将治疗前Conners父母用症状问卷得分与SCORAD积分及主观症状积分(瘙痒与睡眠积分之和)进行相关分析。结果1、本临床观察共纳入36例符合标准的AD患者,采用中药培土清心方内服治疗,结果显示治疗后患者SCORAD积分及主观症状较治疗前均明显下降,差异均有统计学意义(P＜0.01)。2、治疗前AD患者Conners父母用症状问卷积分项目中,男女儿童患者冲动—多动、多动指数均高于中国常模,差异均有统计学意义(P＜0.05),AD儿童品行问题、学习问题、心身问题、焦虑与常模比较差异均无统计学意义(P＞0.05)3、相关分析：男女AD儿童的多动指数与患者主观症状存在中度正相关(男：r=0.610,P＜0.05；女：r=0.533,P＜0.05)；多动指数与SCORAD积分无相关性。4、治疗后,男女儿童患者冲动—多动、多动指数均较前下降,差异均有统计学意义(P＜0.01)；说明培土清心方对于AD多动行为有改善作用,治疗后男女儿童患者冲动—多动、多动指数仍高于中国常模,差异有统计学意义(P＜0.05)。结论1、中药培土清心方内服治疗AD,患者治疗后较治疗前SCORAD积分及主观症状明显下降,差异有统计学意义,验证了培土清心法治疗AD疗效的可靠性。2、AD患者存在多动行为,其中多动指数与主观症状严重程度有关。3、培土清心方在一定程度上能改善AD患者的多动行为。实验研究目的总IgE升高的AD患者存在着n—6脂肪酸代谢的异常,通过检测AD患者治疗前后的n—6脂肪酸水平的变化,探讨培土清心方治疗特应性皮炎可能的作用机理。方法选取血清总IgE升高的AD患者于治疗前及治疗3个月时,以20例健康志愿者为对照,采用ELISA法检测血清中亚油酸(LA)、Y-亚油酸(GLA)、二高亚油酸(DGLA)、花生四烯酸(AA)水平,并将各项血清学指标与患者SCORAD积分进行相关分析。结果1、本临床观察共纳入22例符合标准的AD患者,治疗前AD患者血清中LA水平与正常对照组比较差异无统计学意义(P＞0.05),说明AD患者从饮食中摄入的LA正常,血清中GLA水平均低于正常对照组,差异有统计学意义(P＜0.05),血清中DGLA、AA水平与正常组比较差异无统计学意义(P＞0.05),进一步统计得出GLA/LA水平低于正常对照组,差异有统计学意义(P＜0.05),说明A-6去饱和酶存在缺陷;AA/DGLA水平与正常组比较,差异无统计学意义(P＞0.05),说明△-5去饱和酶功能正常。2、相关性分析：血清GLA与SCORAD积分存在中度负相关(r=—0.528,P<0.05)。血清LA、DGLA、AA水平与SCORAD积分无相关性。3、治疗后患者血清中GLA较治疗前升高,GLA/LA水平较治疗前升高,差异有统计学意义(P＜0.05),说明培土清心方可能对△-6去饱和酶起到了一定的调节作用,从而升高血清GLA水平。结论1、再次证实IgE升高的AD患者n—6必需脂肪酸代谢存在异常,GLA水平的减少是AD发病的机理之一。2、AD患者血清GLA水平与SCORAD积分的相关关系分析结果显示存在中度负相关,提示GLA与AD病情严重程度有关。3、通过培土清心方治疗后,患者血清GLA水平较前升高,GLA/LA水平较治疗前升高,说明培土清心方可能对△-6去饱和酶起到了一定的调节作用,可以升高血清GLA水平,从而起到抗炎及免疫调节作用而缓解病情,推测这可能为培土清心法治疗AD的作用机理之一。更多还原

【Abstract】 BackgroundAtopic dermatitis (AD) is a chronically relapsing and pruritic inflammatory skin disease. Which has a serious effect on patients’physical、psychological and behavior health. The incidence of the disease is steadily increasing in recent years. While no confirmative mechanism of the disease was generally accepted.the western medicine for atopic dermatitis is just to ameliorate symptoms during the flare of the disease, but for the Serious illness, the Efficacy is not well. As an effective treatment, Chinese medicine can not only relieve symptoms but also improve quality of life. So, Chinese medicine has been used to the treatment of atopic dermatitis in clinical and experimental research, therefore Chinese herb for treatment of atopic dermatitis becomes the warm spot due to its unique superiority. Chinese medicine is currently abroad on more in-depth study, the researchers found that a single Chinese medicine or a limited number of extract composition of traditional Chinese medicine are effective, especially the anti-inflammatory and immune regulating role were confirmed. However, in our country, most researches in this field revolve around clinical observation of therapeutic effects by experiential prescription, the specific mechanism remains to be clarified, formula of hilling and clearing away heart-fire for atopic dermatitis has been proved to be effective.which is experience of Professor Chen Da—can for many years in clinical practice. In recent years about the pathogenesis of AD in the immunization studies have made great progress,at the same time, Researchers found that nutrient metabolic factors in the pathogenesis of AD also has an important role, Serum n-6 essential fatty acids levels before and after treatment of the formula were tested to further explore mechanism related to the treatment. As a psychosomatic disease, severe itching, sleep disorders, as well as the Relapse repeatedly have caused tremendous psychological pressure to AD patients, the abnormal behavior is an outward manifestation of Psychosomatic disorders, which also affects the quality of life of patients. therefore, Abnormal behavior gradually attracted people’s attention. we investigate the changes of AD patient in Behavior problems before and after treatment and discuss the effect of the formula of hilling and clearing away heart-fire for atopic dermatitis on behavioral symptoms.Clinical ResearchObjectiveThe purpose of the research was to investigate the behavior problems Of the AD patient, to observe the effects of the formula of hilling and clearing away heart-fire Treatment of atopic dermatitis and its effect on behavioral symptoms.MethodsClinical Observation:patients of 6-11 years old who were diagnosed with atopic dermatitis were selected to this clinical trial. Scores of AD index were collected before treatment and after treatment for three months respectively.The impact on behavior:Behavioral problems were evaluated by the Conners Parent Symptom Questionnaire before and after treatment. Then, compared the index with the Chinese urban norm.The correlation test were calculated to evaluate the correlation between the hyperactivity index and the SCORAD index, between the hyperactivity index and the subjective symptoms index.Results1、36 patients suffered from atopic dermatitis were included to the clinical trial and treated with formula of the Hilling and clearing away heart-fire and adjuvant emollient. SCORAD index was used to evaluated clinical therapeutic outcomes. After treatment, The SCORAD index and Subjective symptoms declined significant (P＜0.01). So it is demonstrates that the method of hilling and clearing away heart-fire had confirmative effects on the atopic dermatitis. 2、before treatment, the impulsivity—hyperactivity index and hyperactivity index of the boys and girls were higher than the norm in China, the differences were statistically significant (P＜0.05).3、Correlation Analysis:there was a moderate positive correlation between hyperactivity index and subjective symptoms index. (boys:r=0.610, P＜0.05; girls:r=0.533, P＜0.05). there was no correlation between hyperactivity index and the SCORAD index.4、After treatment, the impulsivity—hyperactivity index and hyperactivity index of the boys and girls decreased compared with before respectively. The difference was statistically significant respectively (P＜0.05).Which shows the formula of hilling and clearing away heart-fire for the AD can improve hyperactive behavior. The impulsivity—hyperactivity index and the hyperactivity index was still higher than the Chinese norm respectively,The difference was statistically significant (P＜0.05).Conclusions1、The formula of hilling and clearing away heart-fire has confirmative therapeutic effect on AD patients.2、AD patients show hyperactivity behavior. The level of hyperactivity index in AD patients was moderate positive associated with subjective symptom index.3、The formula of hilling and clearing away heart-fire can improve hyperactive behavior of AD patients.Experimental studyObjectiveAD patients with elevated total IgE exist n-6 essential fatty acid metabolism abnormalities. Detect the level of n-6 fatty acid of patients with atopic dermatitis before and after treatment to discuss potential therapeutic mechanisms of formula of hilling and clearing away heart-fire.Methods1、patients who were diagnosed with atopic dermatitis with elevated total serum IgE were selected to this clinical trial. The serum of samples were collected from atopic dermatitis and 20 healthy people. The serum of linoleic acid (LA),γ-linoleic acid (GLA),two high-linoleic acid (DGLA), arachidonic acid(AA) in the patients and health controls were detected by ELISA.2、The Spearman rank correlation test were calculated to evaluate the correlation between n-6 EFA composition and the SCORAD index.Results1、Before treatment, there was no significant difference of LA level between AD patients and control group (P>0.05); serum level of GLA in AD group was lower than the control group, the difference was statistically significant(P <0.01), there was no significant difference of serum levels of DGLA、AA between AD patient and the control group respectively(P>0.05). The GLA/LA ratio was lower than the control group, the difference was statistically significant (P＜0.05), The AA/DGLA ratio not statistically significant between the AD groups and the control group(P>0.05).2、Correlation Analysis:there was a negative correlation between serum level of GLA and the score of SCORAD (r=-0.528, P＜0.05).The SCORAD index did not showed a correlation with serum levels of LA、DGLA and AA (all P>0.05).3、After treatment, the level of serum GLA increased than before, the difference was statistically significant (P<0.01). the GLA/LA ratio was higher than before treatment, the difference was statistically significant(P＜0.05).Conclusions1、It’s demonstrated again in this study that AD patients with elevated total IgE exist n-6 EFAs metabolism abnormality. the lower GLA level is one of the pathogenesis of AD.2、The level of GLA in AD patients is moderate positive associated with the score of SCORAD index. And they also has association with severity of AD.3、The serum level of GLA obviously was elevated after treatment with the formula of hilling and clearing away heart-fire compare with before. The GLA/LA ratio increased, therefore, the formula of hilling and clearing away heart-fire can regulate△-6 desaturase, which may be possible mechanism of treat AD.更多还原