中医药内外合治黄褐斑的疗效观察及抗氧化机理研究
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摘要
目的:
     观察中药内服加消斑膜外用配合耳穴压豆治疗黄褐斑的临床疗效;通过观察其对患者血清SOD、MDA的影响,探讨其可能的治疗机制;通过观察其可能出现的不良事件,对其安全性做出评价。通过以上的研究,为黄褐斑的临床治疗提供一种安全、有效的治疗方案。
     方法:
     1临床部分
     1.1研究设计方法
     采用随机对照方法。用密闭信封法,参照随机数字表按照2:1产生试验组和对照组的随机安排。将对应的治疗分配信笺密封入信封,形成随机信件。按纳入病例的先后顺序将患者随机分配到试验组或对照组。最后纳入研究165例患者,其中试验组112例,对照组53例。
     1.2治疗方法
     试验组112例,肝郁血滞型内服中药消斑1号方及中药祛斑膜1号方外用配合耳穴压豆治疗;肾虚型内服消斑2号方及中药祛斑膜2号方外用配合耳穴压豆治疗。对照组53例,维生素C片和维生素E胶丸口服,0.1%维A酸乳膏外用治疗,治疗12周后进行疗效判定。
     1.3观察方法
     所有患者于初诊、治疗第4周、第8周、第12周复诊时,记录皮损面积、皮损颜色、皮损严重程度评分等观察指标,并于初诊及治疗12周结束时进行血尿常规、肝肾功能等安全指标检测。询问用药依从性,记录合并用药及不良反应。
     1.4疗效判定方法
     ①黄褐斑皮损改变评分方法和标准:根据中国中西医结合皮肤性病学会色素性疾病分会2003年制定的标准。
     ②疗效评价标准:按四级疗效标准评定(尼莫地平法)。
     评分下降指数计算方法:
     下降指数=(治疗前总积分一治疗后总积分)/治疗前总积分。
     1.5安全性评价方法:
     所有患者于试验前后分别检测血常规、尿常规,肝功能、肾功能,记录两组不良事件发生率,临床全过程观察。
     2实验部分
     2.1研究对象:为第二部分中用“中药内服及外用面膜配合耳穴压豆联合治疗”试验组的40例患者;健康对照组10例。
     2.2分别抽取受试者治疗前、治疗后及健康志愿者空腹外周静脉血5ml,注入试管中,离心(2000r/min,10min)吸取上层血清注入EP管中,加盖塞紧,置于-87℃冰箱保存待检,避免反复冻融。
     2.3血清SOD和MDA的检测:采用酶联免疫分析试剂盒检测,严格按照说明书操作。
     3统计学方法
     比较两组的疗效、不良反应采用t检验;多组间的比较采用方差分析;不同疗效及安全性评价采用Ridit分析;有效率的比较采用x2检验。P<0.05具有显著性差异。统计软件为SAS8.1。
     结果:
     1.两组各项症状改善情况的比较:治疗前后两组总评分及下降指数比较有显著性差异(P<0.05)。
     2.两组疗效比较:试验组总有效率87.50%,对照组总有效率66.04%,两组比较差异有统计学意义(P<0.05)。
     3.安全性比较:
     试验组治疗前后实验室检查无异常,试验组和对照组的安全性比较,无显著性差异(P>0.05)。
     4.血清SOD和MDA的水平变化:黄褐斑患者与健康人比较,血清中SOD的水平明显降低,MDA水平明显升高,且差异有统计学意义(P<0.05):试验组治疗后血清SOD水平比治疗前升高,MDA水平比治疗前降低,且差异均有统计学意义(P<0.05);肝郁血滞组与肾虚组比较,肾虚组患者的血清SOD、 MDA水平变化更为显著。
     结论:
     1.中医药“内外合治”黄褐斑的临床疗效肯定。
     2.中医药“内外合治”黄褐斑能升高患者血清SOD水平,降低血清MDA水平。
     3.中医药“内外合治”黄褐斑是一种安全有效的值得推广的治疗方案。
     基于以上结果,本研究初步证实了中医药“内外合治”黄褐斑,疗效肯定,安全性高,值得临床推广应用。同时初步证实中医药“内外合治”黄褐斑可能是通过抗氧化机制发挥作用的。
Objective
     To evaluate the efficacy,safety,efficacy analysis in the treatment of chloasma with Traditional Chinese Medicine Therapy.And study its possible mechanism furtherly.
     Methods
     Clinical research part
     1.Method of the research:The method of random parallel control was used in this clinical trial.All patients with chloasma were randomly assigned to the experiment group and the control group.Using a sealed envelope method,reference randomly arranged in accordance with the2:1to generate the experiment group and the control group.There are165patients which were evaluated by statistics.There are112cases were divided into experiment group and53cases in control group.
     2.Therapeutic method:The test group included112cases.GanYu XueZhi group were treated with NO.1recipel、herbal mask and ear pressure beans. ShenXu group were treated with NO.2recipel、herbal mask and ear pressure beans.The53patients in the control group were treated with the tablet of vitamin C and soft capsule of vitamin E orally,at the same time used0.1dimensional A emulsifiable paste externally. The treatment cycle is12weeks.
     3.Method of the observation:All patients must record the lesion area,color of skin lesions,skin lesions severity score on preliminary diagnosis(before treatment),4,8,12weeks after treatment.And detection of security index of blood and urine routine,hepatic and renal function were performed in all patients before treatment and at the end of12weeks treatments.Meanwhile we should ask the compliance of patients,record the combined medication and side reactions during the experiment. The cured patients were followed up for3months,most patients can use other methods to treat.
     4.Method of evaluation on clinical effect:
     Scoring methods and standards of melasma lesions:According to the standard developed by the skin venereal learn pigmented Diseases Branch of Chinese and Western Medicine in2003.
     Measurement formula:The treatment rate=(pre-treatment score-post-treatment score)/pre-treatment score×100%
     5.Safety evaluation
     The patients'routine blood examination, routine urine examination, ALT, Cr and BUN were measured before and after treatment.The adverse events during the treatment were recorded.
     The experiment part
     l.The research object are40cases in the second part;the control group are10healthy cases.
     2.Extracted fasting peripheral venous blood5ml from the subjects and healthy volunteers before treatment,after treatment.Injected the blood into the test tube, learned from the upper serum and injected into the EP tube after centrifugal (2000/min,10min),plugged,at-87℃refrigeratory quarantine,avoided repeated freezing and thawing.
     3.We use the enzyme league immune analysis test kit to test the levels of SOD and MDA,according to the manual operation strictly.
     Statistical analysis
     Statistical analyses were performed by SAS8.1Test of t and X2statistical methods were used to evaluate the difference between the two groups. The significance was determined as P<0.05.
     Results
     1.The result of the contrast of improving symptoms:The total score and decrease index about lesions of two group patients have significant difference(P<0.05).
     2.The contrast of clinical efficacy:At the12weeks visit viewpoint the total effective rate of the two group is about87.50%and66.04%respectively,there is obvious difference(P<0.05).
     3. The contrast of saefty:There is no significant difference of safety between the two groups(P>0.05).
     4.Changes of serum SOD and MDA before and after treatment about test group:The serum SOD level is increased and the serum MDA level is decreased after treatment,the difference is statistically significant(P<0.05).
     Conclusions
     Traditional Chinese Medicine Therapy in the treatment of chloasma is effective and safe. At the same time, the antioxidant mechanism maybe the reason of the effect of the treatment.Traditional Chinese medicine combined with herb mask and ear pressure beans is a safely,effectively,worthy spreading therapeutic schedule.
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