本文關鍵詞：清熱除濕解毒法治療痤瘡濕熱證及對皮膚生理指標和主要致病菌影響　出處：《北京中醫(yī)藥大學》2016年博士論文　論文類型：學位論文

  更多相關文章： 痤瘡丙酸桿菌 丹參酮膠囊 療效評價 皮膚生理指標 清熱除濕湯 濕熱證 尋常痤瘡

【摘要】：背景痤瘡是皮膚科常見病,發(fā)病率高,涉及青春期前后各年齡階段。本病常反復發(fā)作,臨床實踐證明,中藥復方能夠全面調整身體機能,從而取得良好的效果。以清熱除濕湯為代表的清熱除濕解毒類中藥常用于治療急性濕熱性皮膚病。不同疾病在其發(fā)展過程中可以出現(xiàn)相同的證,即可采取“異病同治"的方法。對于濕熱型痤瘡的治療,也是根據證的表現(xiàn),而應用清熱除濕湯治療,臨床取得較好的療效。痤瘡的病因復雜,發(fā)病機制涉及遺傳、免疫、內分泌、微生物感染、毛囊皮脂腺導管角化等多方面因素。目前尚缺乏中醫(yī)藥治療在皮膚屏障功能修復以及皮膚生理指標改善方面的研究。本研究基于清熱除濕解毒類中藥對濕熱型痤瘡的治療探索中醫(yī)藥在改善皮膚微環(huán)境方面的作用。目的(1)觀察痤瘡患者皮損和中醫(yī)證候的改善情況,客觀性評價清熱除濕解毒類中藥治療濕熱型痤瘡的臨床療效,為指導臨床規(guī)范化辨證分型治療,推廣應用奠定基礎。(2)結合痤瘡患者皮膚生理指標的檢測結果及對痤瘡主要致病菌的抑制研究,為清熱除濕解毒類中藥治療痤瘡及預后評估提供數(shù)據支持。方法(1)臨床療效及安全性評價本研究采用隨機、對照的試驗設計,評價清熱除濕湯對于痤瘡濕熱證的臨床療效。以2：1比例隨機納入72例濕熱型痤瘡患者,試驗組48例,給予清熱除濕湯治療,對照組24例,給予丹參酮膠囊治療。療程4周。觀察痤瘡皮損和臨床綜合證候的改善情況評定療效,記錄不良反應發(fā)生情況,進行安全性評價。(2)皮膚生理指標測定應用VISIA面部圖像分析系統(tǒng)和SOFT5.5皮膚檢測儀測定受試者面部紅色區(qū)、棕色斑、毛孔、紫質和皮膚水分含量、皮膚油脂、PH數(shù)值,以治療前后和每次復診時作為檢測時點,從不同時間節(jié)點皮膚生理指標的檢測數(shù)據,動態(tài)反映皮膚屏障功能的修復情況,以客觀數(shù)據資料為依據說明中藥對于不同皮膚生理指標所起到的調節(jié)作用,最終對皮膚表面微環(huán)境的改善產生的影響,揭示特定皮膚生理指標改善與中藥治療的相關性。(3)中藥抑菌研究痤瘡患者毛囊、皮脂腺中存在多種微生物,抑制其生長可以使痤瘡病情得到緩解。本試驗將痤瘡丙酸桿菌標準菌株進行進一步傳代培養(yǎng),進行體外抑菌試驗研究,以不同濃度的清熱除濕湯為試驗藥物,為臨床應用提供實驗室依據。結果(1)臨床療效及安全性評價結果清熱除濕湯治療濕熱型痤瘡患者,臨床痊愈16.28%,顯效30.23%,有效39.53%,無效13.95%,愈顯率(痊愈+顯效)為46.51%,總有效率(痊愈+顯效+有效)為86.04%。對照組丹參酮膠囊治療尋常痤瘡患者,臨床痊愈9.52%,顯效19.05%,有效28.57%,無效42.86%,愈顯率為28.57%,總有效率為57.14%。試驗組的皮損消退率為62.86%,綜合證候療效率為62.41%,優(yōu)于對照組,具有統(tǒng)計學意義,說明清熱除濕湯對改善皮損和中醫(yī)臨床證候方面優(yōu)于對照組。對兩組受試患者療前、療后進行安全性實驗室檢查,經觀察試驗組中5例患者血肌酐、尿素氮略低于正常。對照組中3例患者出現(xiàn)尿素氮偏低,4例出現(xiàn)尿白細胞±,但無尿頻尿急尿痛等不適。試驗組中4例患者服藥后出現(xiàn)輕度胃腸道反應、對照組中有1例患者,均以胃脘不適及輕度腹瀉為主,調整用藥方式后即緩解。(2)皮膚生理指標測定結果治療后試驗組的紅色區(qū)和棕色斑分值較對照組減少,具有統(tǒng)計學意義,研究結果顯示,清熱解毒除濕類中藥有較好的改善皮膚炎癥和皮膚棕色斑的作用,其療效優(yōu)于對照組。治療前后紫質和毛孔的分值減少無統(tǒng)計學意義,說明兩組藥物在改善紫質和毛孔方面效果不明顯。治療后試驗組皮膚油脂含量為18.74±10.263,較對照組(23.90±12.498)數(shù)值減少,雖不具有統(tǒng)計學意義,但說明清熱解毒除濕類中藥在改善皮膚油脂含量方面有一定優(yōu)勢。治療結束后,兩組痤瘡患者的皮膚水分含量和PH數(shù)值對比顯示無顯著性差異(P0.05),說明兩組藥物在改善皮膚水分和PH值方面療效相當。(3)中藥抑菌研究結果采用試管稀釋法進行清熱除濕湯對痤瘡丙酸桿菌的抑菌試驗研究。將P.acne標準株進行轉種培養(yǎng)后,中藥倍比稀釋后進行抑菌作用的研究。經72h厭氧培養(yǎng)后,各試管中的中藥從1：2進行倍比稀釋,在藥物濃度為500mg/ml時可見細菌生長,即清熱除濕湯的最小抑菌濃度為500mg/ml。在同體積相同實驗條件下進行定量接種,結果顯示清熱除濕湯對痤瘡丙酸桿菌有抑制作用,菌落計數(shù)為1500CFU/ml。結論(1)清熱除濕湯治療濕熱型痤瘡有較好效果,在改善皮損情況和綜合證候方面療效優(yōu)于對照組,值得臨床推廣應用。(2)清熱除濕湯在改善痤瘡患者的皮膚水分、油脂、紅色區(qū)、棕色斑方面有一定作用。提示我們在臨床診療過程中,要注意皮膚屏障的保護和修復從而達到治療痤瘡的目的。(3)清熱除濕湯在濃度為500mg/ml時可見細菌生長,說明試驗藥物對痤瘡丙酸桿菌有一定抑制作用,但與以往文獻報道的相關中藥比較,其抑菌作用偏弱。在進一步定量接種實驗中顯示,清熱除濕湯對痤瘡丙酸桿菌具有明確的抑制作用,菌落計數(shù)為1500CFU/ml,明顯少于對照管中的細菌數(shù)量。此種情況可能與藥物的整體調節(jié)作用有關,而對于皮膚表面的致病菌,單純應用內服藥物只能起到一定的抑制作用。
[Abstract]:Background: acne vulgaris is a common disease in Department of Dermatology, the incidence rate is high, the age of puberty involved. The disease often repeated attacks, clinical practice has proved that the medicine can fully adjust the body function, so as to achieve good results. Qingrechushi detoxifying herbs in qingrechushi Tang on the commonly used in the treatment of acute exudative skin disease. The disease can appear the same card in its development process, can take "different diseases". For the treatment of damp heat type acne, but also according to the certificate of performance, and the application of qingrechushi decoction has a better clinical curative effect. The cause of acne pathogenesis is complex, involving genetic, immune, endocrine, microbial infection many factors, such as keratinized pilosebaceous duct. There is still a lack of treatment of traditional Chinese medicine research in the repair of skin barrier function and skin physiology index based on the improved. The treatment of Chinese traditional medicine on detoxification of heat and dampness heat type acne to explore Chinese medicine to improve the skin micro environment to effect. (1) observed in patients with acne lesions and TCM syndromes, clinical efficacy evaluation objectivity qingrechushi antidotal traditional Chinese medicine for treating damp heat type acne, for guiding clinical standardization of syndrome differentiation treatment, laid the foundation of application. (2) study on inhibiting the binding of test results in patients with acne and acne skin physiological index of main pathogenic bacteria, to provide data support for the evaluation of qingrechushi detoxifying herbs for the treatment of acne and prognosis. Methods (1) the clinical efficacy and safety evaluation of the randomized, controlled clinical trial design. Evaluation of curative effect of Qingre Chushi Decoction for acne of damp heat syndrome. 2:1 were randomly enrolled 72 patients with damp heat syndrome of acne patients, 48 cases of experimental group, given qingrechushi decoction, 24 cases in the control group, to To Danshentong Capsules for treatment. The treatment course of 4 weeks. The improvement of curative effect observation of acne lesions and clinical syndromes, record the occurrence of adverse reactions, the safety evaluation was carried out. (2) the determination of test subjects face red zone, the application of VISIA facial image analysis instrument detection system and SOFT5.5 skin physiological index of skin brown spots, pores numerical and skin moisture content, porphyrin, skin oils, PH, before and after the treatment and at every visit as the detection point, from the test data of different time node skin physiology index, reflecting the dynamic skin barrier repair, with objective data illustrate the regulatory effect of traditional Chinese medicine for different skin physiological indexes play finally, effects of the skin surface micro environment produced by correlation to reveal the specific physiological indexes of skin and traditional Chinese medicine treatment. (3) traditional Chinese medicine antibacterial research of acne hair follicle There are a variety of microorganisms, sebaceous glands, can inhibit the growth of the acne remission. The standard of Propionibacterium acnes strains were further subcultured to study the antibacterial test in vitro, with different concentrations of Qingre Chushi Decoction for drug testing, and provide laboratory evidence for the clinical application. Results (1) the results of clinical evaluation safety and qingrechushi Decoction in the treatment of damp heat type acne patients, 16.28% cured, 30.23% markedly effective, 39.53% effective, 13.95% ineffective, markedly effective rate (cure + markedly) was 46.51%, the total effective (cure and significant effect and effective) to 86.04%. control group Danshentong Capsules in the treatment of acne vulgaris, 9.52% cured, 19.05% markedly effective 28.57%, invalid 42.86%, the effective rate was 28.57%, the total efficiency of 57.14%. lesions in experimental group, remission rate was 62.86%, syndrome treatment efficiency of 62.41%, better than the control group, with statistical significance, That qingrechushi Decoction to improve the skin lesions and TCM syndrome than the control group. The two groups of patients before treatment, after treatment for safety of laboratory examination, the observation group in 5 cases of patients with serum creatinine, urea nitrogen is slightly lower than the normal control group. 3 cases had low blood urea nitrogen, 4 cases there were white blood cell, but no frequent micturition discomfort. Mild gastrointestinal reaction occurred in the experimental group of 4 patients after treatment, 1 patients in the control group, both with epigastric discomfort and mild diarrhea, adjust medication after remission. (2) the skin physiological index determination results after treatment the test group of red and brown spot area score decreased than the control group, with statistical significance, the results of the study show that Chinese medicine has Qingrejiedu dehumidification can improve skin inflammation and skin brown spot, its effect is better than the control group before and after treatment. The pores and porphyrin. The scores decrease was not statistically significant, indicating that two groups of drugs is not obvious in improving the effect of porphyrins and pores. The experimental group after treatment of skin fat content is 18.74 + 10.263, compared with the control group (23.90 + 12.498) values to reduce, although not statistically significant, but that detoxification has certain advantages in traditional Chinese medicine in improving wet the skin grease content. After the end of treatment, the skin moisture content and PH value were compared between the two groups of acne patients showed no significant difference (P0.05), two groups of drugs in improving skin moisture and pH effect. (3) Chinese medicine inhibitory results by test tube dilution method was used to study the bacteriostatic test of Qingre Chushi Decoction on acne Propionibacterium. P.acne standard strains to culture, traditional Chinese medicine research dilution after inhibition by 72h. Anaerobic culture, traditional Chinese medicine in vitro from 1:2 were diluted in. The drug concentration for visible growth of bacteria 500mg/ml, the minimal inhibitory concentration of Qingre Chushi Decoction for 500mg/ml. in the same volume under the same experimental conditions for quantitative inoculation, results showed that qingrechushi decoction can inhibit the Propionibacterium acnes, colony count of 1500CFU/ml. (1) conclusion qingrechushi Decoction in the treatment of damp heat type acne has good effects in improving skin lesions and syndromes has better effect than the control group, it is worthy of clinical application. (2) qingrechushi Decoction in improving skin moisture, acne oil, red, brown spots have a certain effect. We suggest that in the process of clinical practice, pay attention to the protection and repair of the skin barrier to the treatment of acne. (3) qingrechushi Decoction in the concentration of visible growth of bacteria 500mg/ml, indicating the experimental drug has inhibitory effect on Propionibacterium acnes, but with previous report Comparison of the antimicrobial effect of traditional Chinese medicine, weak. Shown in further quantitative inoculation experiments, qingrechushi decoction has marked inhibitory effects on Propionibacterium acnes, colony count was 1500CFU/ml, significantly less than the number of bacteria in such a situation. Take care of drugs may be related to the whole regulation function, and the pathogenic bacteria on the skin surface, simple the application of oral drugs can play a certain effect.

【學位授予單位】：北京中醫(yī)藥大學
【學位級別】：博士
【學位授予年份】：2016
【分類號】：R275.9

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