【作者】 吴小红；

【导师】 刘瓦利；

【作者基本信息】 中国中医科学院 ， 中医外科学， 2010， 博士

【摘要】 研究目的：①女性黄褐斑患者易感因素及中医证候本质的探索。②应用计算机数字图像分析系统(皮肤镜)评价滋肾化斑汤治疗女性黄褐斑的临床疗效；研究方法：临床研究采用①临床问卷调研的方法分析女性黄褐斑患者的易感因素和中医证侯。②随机、平行对照的研究方法观察滋肾化斑汤的临床疗效和安全性,采用皮肤镜对其疗效进行客观评价。40例治疗组患者给予中药滋肾化斑汤方口服,2次/天；30例对照组患者给予口服维生素C200mg,3次/天,维生素E100mg,3次/天。两组患者均外用丝白去斑软膏,12周为一个疗程。研究结果：临床对130例女性黄褐斑患者的临床资料分析显示,本病的发病年龄多在20-50岁之间,以30-40岁年龄段患者最多,约占53.1%；皮损特点以两颊为主,呈蝶形分布者49例(37.7%)；其中面部皮肤为干性者多见,63例(48.5%)。易感因素分析结果显示,首先精神(包括工作压力大、精神紧张或者焦虑、抑郁)及睡眠不佳等因素与黄褐斑的发病有明显关系,有精神因素者88例(占67.7%)；其次妊娠、口服避孕药是黄褐斑的另一重要诱发因素。月经不调者111例(占85.4%)(包括痛经、颜色发暗、先期、后期、先后无定期等)；伴有明确的妇科疾病者53例(占40.8%)如妇科炎症、肿瘤等；经常服用避孕药、流产以及妊娠有关者36例(27.7%)。再次为日晒及光辐射,发生及(或)加重与日光相关,或者长期在强烈灯光及电脑前工作者64例(49.2%)。有遗传倾向者有39例(占30.0%)。由于不当化妆品及美容引起黄褐斑者24例(18.5%)。此外,一些因素,如面部伴发色素痣、雀斑者62例(47.7%)；伴发其他面部皮肤病者71例(54.6%),其中痤疮38例,脂溢性皮炎、湿疹、荨麻疹者29例,扁平疣2例,白癜风2例；中医证侯分析结果显示辩证为肾虚血瘀证者82例(63.1%),肝郁气滞者71例(54.6%),脾虚湿盛者29例(22.3%),其中大部分患者肾虚兼有肝郁症状,多为虚实夹杂。70例患者完成服药观察者65例,其间因各种原因脱落者5例(<20%)。其中治疗组38例患者经过12周的中药滋肾化斑汤治疗,临床痊愈5例(13.2%),显效22例(57.9%),有效9例(23.7%),无效2例(5.3%),显效率为71.1%。27例对照组患者口服维生素C、E治疗12周,临床痊愈2例(7.4%),显效8例(29.6%),有效13例(48.1%),无效4例(14.8%),显效率为37.0%。两组疗效比较,差异显著(P<0.05)。治疗组和对照组患者治疗前后皮损L*、a*、b*值及ITA。值有显著变化,差异有统计学意义(P<0.01)。治疗组治疗前后皮损L*、a*、b*值及ITA。值变化明显高于对照组,有显著差别(P<0.01)。结果表明,滋肾化斑汤治疗女性黄褐斑疗效显著,明显优于口服维生素C、E的对照组。无严重不良反应和不良事件。讨论：’黄褐斑病因复杂,目前普遍认为可能与内分泌失调、遗传、化妆品、氧自由基、紫外线照射、精神紧张等多种因素相关。本组研究的130例女性黄褐斑患者临床资料分析显示,本病的发病年龄30-40岁年龄段患者最多,皮损以两颊为主,呈蝶形分布,其中面部皮肤以干性者多见。易感因素分析结果显示,结果显示精神(包括工作压力大、精神紧张或者焦虑、抑郁)及睡眠不佳等因素与黄褐斑的发病有明显关系,其次与妊娠、服用避孕药、月经不调(包括痛经、颜色发暗、先期、后期、先后无定期等)及妇科疾病等内分泌因素关系密切。再次紫外线照射、遗传以及化妆品及美容不当与黄褐斑发病有关。此外,面部有雀斑及色素痣的患者好发黄褐斑,可能与其面部黑素细胞较多有关。面部炎症及其他问题皮肤也易发黄褐斑。可能与炎症容易引起黑素细胞生成有关。从中医证候调查分析显示,烦躁易怒者、睡眠不佳、经前乳房胀痛、目花、目涩及耳鸣耳聋、腰脊酸痛、月经量少及经色暗黑痛经者、大便干燥者所占比例较高,中医学认为妇人以血为用,阴血为精神、神志的物质基础,阴血不足可见患者失眠多梦、烦躁易怒、腰背酸痛、形寒肢冷、经血减少及神疲乏力等虚证。阴血不足,失其濡润作用可见目涩、大便干燥等。调查结果显示辩证为肾虚血瘀证者最多,其次为肝郁气滞证者,也有少部分属脾虚湿盛证者。其中大部分患者肾虚兼有肝郁症状,多为虚实夹杂。这与古代文献阐述的黄褐斑由“水亏不能制火,血弱不能华肉以致火燥结成斑黑,色枯不泽而成”相一致。我们采用滋肾化斑汤对38例女性黄褐斑患者治疗12周,结果治疗组显效率明显高于口服维生素C、E的对组照,差异显著(P<0.05)。皮肤镜观察结果显示两组治疗前、后皮损部位L*值、a*值、b*值及ITA°值变化显著,差异具有统计学意义(P<0.01)。L*值代皮肤亮度,测量肤色时主要受皮肤中黑素的影响。两组患者治疗后皮损部位的L*值均高于治疗前,且差异显著(P<0.01)。a*值反映皮肤红绿色变化,主要受皮肤中血红蛋白氧合程度或血液循环状态的影响。两组治疗后皮损部位的a*值低于治疗前,且差异显著(P<0.01)。b*值反映皮肤黄蓝色变化,受皮肤中黄色素和脂色素影响较大,两组治疗后皮损部位的b*值低于治疗前,且差异显著(P<0.01)。ITA°值(颜色个体类型角),代表色度总体变化情况,ITA°值越大,肤色越浅。治疗组及对照组治疗后皮损部位的ITA°值均高于治疗前,且差异显著(P<0.01)。,而治疗组皮损部位L*值、a*值、b*值及ITA°值变化明显高于对照组,有显著差别(P<0.01)。结果表明,滋肾化斑汤治疗女性黄褐斑疗效显著,明显优于口服维生素C、E的对照组。皮肤镜观察显示滋肾化斑汤可以通过减少黄褐斑皮损部位的黑素含量来改善皮肤的亮度、通过减轻黄褐斑皮损部位的毛细血管扩张程度来改善色斑、通过减轻黄褐斑皮损部位的黄色素和脂色素来改善色斑,达到治疗黄褐斑的目的。并且中药滋肾化斑汤对减少皮损部位的黑素含量、减轻皮损部位的毛细血管扩张程度以及减轻皮损部位的黄色素和脂色素等疗效也明显优于口服维生素C、E的对照组。治疗过程中发现病程越短,年龄越小,疗效越好；而治疗时间越长,疗效越显著,因此,需要开发一些疗效好、服用方便的丸、散、膏及片剂,以便临床长期服药,从而提高疗效。滋肾化斑汤主要由山萸肉、菟丝子、生地黄、当归、川芎、僵蚕、柴胡、白芍、白蒺藜、丹参、酒军、红花、茯苓、白术、珍珠母、桂枝等组成。其中山萸肉、山药、菟丝子、生地黄等为君药,具有平补肝肾作用,当归、川芎、僵蚕、丹参、白芍、红花等养血活血消斑,配合柴胡、白蒺藜、酒军清肝祛风泻热,茯苓、白术健脾除湿,稍佐桂枝具有温经通络消斑之意。目前中医药方法治疗黄褐斑文献众多,但对其疗效评价,大多采用肉眼观察的方法,缺乏客观性。皮肤镜应用多光谱皮肤显微偏振光与数字图像处理技术,把采集到的真彩色皮肤图像信号转化成数字信号,再进行分析和处理,能客观、准确计算出皮损形状及颜色,客观性及重复性好,灵敏度高,能避免了肉眼观察和个体判断差异等缺陷,为临床疗效判断提供客观依据。综上所述,黄褐斑发病可能与内分泌、精神因素、紫外线照射、化妆品使用不当及遗传等因素相关,中医认为多为肝肾阴虚,瘀血阻络。中药滋肾化斑汤具有滋肾清肝,活血消斑功效。治疗女性黄褐斑效果显著,其远期疗效和进一步的作用机理值得深入研究。皮肤镜能避免了肉眼观察和个体判断差异等缺陷,为临床疗效判断提供可靠的客观依据。使结果更真实、更客观,是色素疾病一个比较好的评价方法,值得临床推广使用。更多还原

【Abstract】 Objective:①The analysis of predisposing factor and entity of a crowd of symptoms in Traditional Chinese Medicine(TCM) of female chloasma from clinical data.②To evaluate the efficacy and safety of zi-shen and hua-ban herbal decoction for the treatment of patients with female chloasma by dermoscope.Methods:①The subject adopted clinical-answer-sheets to analysis the predisposing factors and entity of a crowd of symptoms in TCM of female chloasma patients;②Adopted the opening, random and parallel contrast methodology to observe the clinical effect and safety of the zi-shen and hua-ban herbal decoction. The pigmentation of skin lesions was measured by a dermoscope, namely MicroskinⅡmultifunction system with polarizing microscope and digital image.Forty patients of therapy group with chloasma took the zi-shen and hua-ban herbal decoction orally twice daily for 12 weeks. And sixty patients of contrast group took Vitamin C and Vitamin E orally,the dose was 200mg and 100rrig respectively, three times a day.Both groups were topically treated with Si-Bai-Qu-Ban ointment twice daily and twelve weeks were needed for a course.Results and Discussion:The clinical data from 130 female chloasma patients shows that the age of the episode is between twenty and fifty years old,especially the patients of thirty to fouty is at most, which reached 53.1%; The patients with skin lesions of butterfly distribution was 49,which reached 37.7%. Among them 63 patients have dry face skin,which reached 48.5%.Firstly,the results of predisposing factors shows that tension,stress,sleepless and morosity are relevant with the onsets of chloasma significantly,there are 88 patients with Psychic factors,which reached 66.7%;Secondly,the factor of cyesis and oral contraceptives are another important evoking agents. There are 111 patients with menoxenia,which reached 85.4%; There are 53 patients who have the diagnosis gynecological disease,including Phlegmasia, cancers,and so on, which reached 40.8%; There are 36 patients of oral contraceptives usually, induced abortion and cyesis,which reached 27.7%. Thirdly,the solarization is also relevant with the chloasma.There are 64 patients who are wordking in sunlight,the fierce lamplight or the computer radiations, which reached 49.2%. There are 39 patients with family history.The tendency to heredity is about 30.0%. There are 24 patients with the cosmetic history and cosmetics of poor quality, which reached 30.0%;Besides,the factors such as nevus, freckles and another face dermatogic diseases such as acne, dermatitis,eczema,urticaria,verruca plana,vitiligo and so on are correlation with the episode.According to dialectical in TCM, the entity of a crowd of symptoms in TCM of female chloasma patients shows that there are 82 patients with the Shen-xu-xue-yu symptoms which reached 63.1% and 71 patients with the Gan-yu-Qi-Zhi symptoms, which reached 54.6% and 29 patients with the Pi-xu-shi-yun symptoms, which reached 22.3%.Above them,more patients have the both shen-xu and gan-yu symptoms in TCM, the entity of the crowd of symptoms in TCM is mixed with weakness and enriched evils.There are 65 patients who had finished the trial and 5 patients who had been absent(<20%).The average effective rate of thirty-eight therapy patients with chloasma was 71.1% 12 weeks later,which is more effective than the contrast group (P<0.05),that the average effective rate of twenty-seven contrast patients was 37.0%. In both of the groups, the values of L*,a*, b* and ITA°(Individual topology angle) showed statistical differences (P<0.01) before and after treatment. However, the change of L*,a*, b* and ITA°in the therapy group showed more statistical differences (P<0.01) than in the contrast group. No adverse effect was found during the study.Conclusion:The zi-shen and hua-ban herbal decoction is effective and safe in chloasma. The herbal prescription was consist of dodder seed,rehmannia dride rhizome,angelica,zechwan lovge rhizome,thorowax root,peony root,Caltrop, safflower,tuckahoe,largehead atractylodes rhizome,cassia twig,and so on. It has the effect of invigorate-kindey, Liver and moving blood.It can reduce the amount of melanin in the lesions, yellow pigment and lipochrome, and relieve the extent of telangiectasis in pigmented areas.The dermoscope has the character of no wound, objectively,exactly without individual judgement difference by eye-observe in evaluating the clinical effect.It is worthing of spreading.更多还原