清热祛瘀法治疗银屑病的疗效及其对细胞因子网络的影响
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摘要
银屑病(Psoriasis)俗称“牛皮癣”,相当于中医学的“白疕”,是皮肤科一种常见的具有特征性的慢性复发性炎症性皮肤病,皮损表现为红色斑丘疹上覆盖多层银白色鳞屑。我国的男性患病率高于女性,城市患病率高于农村,北方发病率高于南方。在自然人群中的发病率为0.1-3%,大多有明显的季节性,在白色人种中患病率高,其次为黄种人,黑种人较少。中医认为本病的发生与外邪入侵,七情内伤,脾胃失和等导致血热、血虚、血瘀而导致本病反复发作。西医认为本病发生发展的主要原因或诱因有遗传因素、感染、代谢障碍、内分泌因素、免疫因素、精神因素等。
在总结前从经验的基础上,我们结合岭南气候湿热多变特点,从瘀热互结的角度出发,对中医“从血”论治银屑病进行了多方面的探讨,认为银屑病系血热内蕴,郁久化毒,以致血热毒邪外壅肌肤而发病,热毒入里,耗伤津液,瘀滞气血,其发展变化的不同阶段病理变化虽各有不同,但均有热、瘀的病理特点,瘀热互结贯穿疾病的全过程。据此以《伤寒论》太阳病蓄血证瘀热互结证治为指导,制定清热祛瘀中药复方,通过临床和实验研究探讨其治疗银屑病的疗效及其作用机理。
全文包括文献综述和研究报告两部分。
文献综述包括两部分。第一部分综述中医药治疗银屑病的临床与研究进展,包括银屑病的历史沿革,近代及现代医家对银屑病病因病机的认识,以及中医内外治方法及近年的临床及实验研究进展。第二部分综述了银屑病的西医临床与研究进展,由于本病的病因及发病机制均未明确,临床缺乏有效的治愈手段,故本病一直是皮肤科领域内的研究重点及难点,至今尚未有肯定结论,综述包括了流行病学、病因及发病机制、治疗等方面。
研究报告包括临床研究和实验研究两部分。
临床研究通过清热祛瘀复方治疗银屑病血热证的临床验证,探讨中药复方治疗银屑病血热证的临床疗效,由广州中医药大学第一附属医院皮肤科临床研究的完成。
在清热祛瘀复方治疗银屑病血热证临床验证中,共选取银屑病血热证78例,其中治疗组40例,雷公藤多甙片对照组38例,两组性别、年龄、病程、皮损形态、治疗前PASI评分、中医临床症候症状评分差异无统计学意义(P＞0.05),具有可比性。
结果显示:治疗组及对照组治疗前后PASI评分比较具有显著性差异(P＜0.05),治疗后两组PASI评分比较无统计学意义(P＞0.05)。两组总体疗效经经卡方检验比较差异无统计学意义(P＞0.05);说明清热祛瘀复方与雷公藤多甙片总体疗效相当。清热祛瘀复方明显改善患者皮肤瘙痒、心烦、口渴、便秘、尿黄、舌象、脉象等中医临床症候。结果表明中药复方治疗寻常型银屑病血热证有较好疗效。尤其对心烦、口渴、大小便等中医临床症状均具有良好疗效。
实验研究包括三部分:
实验研究一:利用雌激素期增生的小鼠阴道上皮模型研究清热祛瘀复方抑制增殖作用。昆明种雌性小鼠随机分为6组:中药复方小、中、大剂量组(1、2、3组)、雷公藤多甙组(4组)、雷公藤多甙+中药组(5组)、阴性对照组(6组)。在此项实验中,阴性对照组与雷公藤对甙组比较有极显著差异(P＜0.05),阴性对照组与小剂量中药组、大剂量中药组及雷公藤对甙+中药组比较也有显著差异(P＜0.05)。中药各组与雷公藤多甙组比较发现,中药中剂量组与雷公藤多甙组比较有显著差异(P＜0.05),中药小、大剂量组,及雷公藤多甙+中药组与雷公藤多甙组比较差异无统计学意义(P＞0.05)。
实验研究二:利用小鼠尾鳞片表皮模型研究清热祛瘀复方促进分化的作用,C57小鼠分组同上,在此项实验中,大中药组与阴性对照组相比有统计学意义(P＜0.05),但并没有促进小鼠尾部鳞片表皮颗粒层的形成。雷公藤多甙组与阴性对照组相比无统计学意义(P＞0.05)。并且用药的5组都没有显著促进小鼠尾部鳞片表皮颗粒层的形成。
实验三:利用CBA技术观察中药复方对银屑病动物模型细胞因子网络的影响。上述二组小鼠各取12份血清样本(昆明种每组取6只,C57小鼠每组取6只,♀♂各半)。6组外周血中IL-1R、IL-2、IL-5、IL-6、IL-10、TNF-a的水平并无统计学意义。而不同组别小鼠血清中IFN-γ、GM-CSF、IL-17、IL-4水平有统计学意义,且在某些剂量中药用药组都有不同程度的升高。
研究表明祛清热祛瘀复方临床治疗银屑病血热证安全有效,简便易行;该药具有明显抑制实验小鼠阴道上皮细胞增生过快,提示该药能抑制银屑病表皮增生过快;其次,清热祛瘀复方能提高小鼠血清中IFN-γ、GM-CSF、IL-17、IL-4水平,提示该药治疗银屑病可能是多种细胞因子相互作用的结果,而不是单个细胞因子的简单升降所引起的,但其机理仍有待进一步研究,且剂型亦有待改善。
Psoriasis,which is commonly called "niupixuan" and called "baibi" in traditional Chinese medicine,is the common chronic recurrent inflammatory dermatoses,and its skin lesions appearance is red maculopapule covered multilayer argentate scale.Its prevalence of male is higher than female,its prevalence in city is higher than in country,and its prevalence in north is higher than in south.The prevalence in nature population is about 0.1-3%, which has obvious seasonality.The prevalence in the white race is highest and lowest in melanian and modera in xanthoderm.It is believed in our Chinese medicine that the occurrence of psoriasis is related with blood heat,blood deficiency and blood stasis which caused by invasion of exogenous evil, internal injury caused by excess of seven emotions,estrangement of spleen and stomach and so on.Meanwhile it is believed in western medicine that the main reasons or inducement of its occurrence and development are genetic factor, infection,dysmetabolism,endocrine secretion factor,immunity factor,spirit factor and so on.
On the basis of before experience summary,considered the characteristics of lingnan climate,from the angle of stagnation of blood stasis and heat, exploring the "from heat" treatment of psoriasis in many ways,it is believed that psoriasis is caused by intrinsic blood heat which turns into toxic because of long time stagnation,and its leads to the toxic evil of blood heat outward to skin and muscle and causes the disease.Heat toxic invading inward which leads to depletion of body fluid and stagnation of Qi and blood is the pathological change of different stage of psoriasis developing and changing, though it is different,the pathological characteristics has heat and blood stasis,and stagnation of blood stasis and heat breaks through the wholes process.Because of that,we followed the guidance of the principle of treating stagnation of blood stasis and heat of Taiyang syndrome of blood stasis of《Treatise on Cold-induced Febride Diseases》,worked out the Chinese herbal compound which has the action of clearing heat and removing blood stasis,and explored the curative effect and mechanism of action of treating psoriasis by the clinical and experimental study.
This article is divided into two parts.One is literature review and the other is research report.
Literature review includes two parts.The first one,Traditional Chinese clinic and research development on the psoriasis,includes its successive changes,the opinions of neoteric doctors on its pathogenesis and medical and surgical treatment.The second one is modern clinic and research development on the psoriasis.It gains special concerns of the academic circles' owing to its unknown etiological factors and pathogenesis.Besides,it is scarce of effective therapeutic tools.Considerable research has been performed on epidemiology,etiological factors,pathogenesis,and therapy in recent years.
The research report includes two parts.One is about clinical research, and the other is about experimental one.
Clinical verification on blood-heat syndrome of psoriasis treated by Chinese herbal compound with the action of clearing heat and removing blood stasis was performed and clinical effect was explored.And the clinical research was completed by departmrnt of dermatology of the first affiliated hospital of Guangzhou university of traditional Chinese medicine.
In clinical verification on blood-heat syndrome of psoriasis applyed with Chinese herbal compound with the action of clearing heat and removing blood stasis,78 cases with blood-heat syndrome were selected and 40 cases applied with Chinese herbal as treatment group and 38 cases applied with Tripterygium Wilfordii tablet for controlled group.The two groups had comparability because there were no significant deviations in the sex,age,course of disease,shape of skin destruction,PASI score before treatment,syndromes score between them.
Results showed that there was significant difference of PASI score before and after the treatment in both groups(P＜0.01).There was no significant difference of PASI score after the treatment in both group(P＞0.05).And there was no significant difference of general efficacy between the two groups(P＞0.05),which indicated that the both are effective.Chinese herbal compound with the action of clearing heat and removing blood stasis could improve clinical symptoms of Chinese medicine such as itch of skin,upset, thirsty,constipation,yellow urine,tongue picture,pulse demonstration and so on.And the results showed that there was better efficacy using Chinese herbal compound with the action of clearing heat and removing blood stasis treating ordinary blood heat syndrome of psoriasis,especially in clinical symptoms of Chinese medicine such as upset,thirsty,urine and stool and so on.
Experimental research includes three parts:
Experimental researchⅠ:The model of proliferative vaginal epithelial cells of mice in estrogen cycle was used to study the prohibition efficacy of Chinese herbal compound with the action of clearing heat and removing blood stasis.Kunming female mice was randomly divided into six group:small,medium and large doses groups of Chinese herbal(groupl,2,3),tripterygium glycosides group(group4),tripterygium glycosides plus Chinese medicine group (group5) and negative control group(group6).In the experimental research, there was statistical difference between negative control group and tripterygium glycosides group(P＜0.05),between negative control group and small doses group of traditional Chinese medicine,large doses group of traditional Chinese medicine,and tripterygium glycosides plus Chinese medicine group.It was found that there was statistical difference between medium doses group of traditional Chinese medicine and tripterygium glycosides group(P＜0.05),and there was no differencein tripterygium glycosides group compared with small doses group of traditional Chinese medicine,large doses group of traditional Chinese medicine,and tripterygium glycosides plus Chinese medicine group(P＞0.05).
Experimental researchⅡ:The model of the scale epidermis cells of mice tail was used to study the promoting differentiation efficacy of Chinese herbal compound with the action of clearing heat and removing blood stasis.C57 mice Groups were divided as above.In the experimental research,there was statistical difference between negative control group and large doses group of traditional Chinese medicine(P＜0.05),but it dose not promote the formation of the scale epidermis cells of the tail.there was no difference between tripterygium glycosides group and negative control group(P＞0.05).the promoting function of formation of the scale epidermis cells of the tail was not obvious in five groups with drugs.
Experimental researchⅢ:CBA technique was used to observe the influence on cytokine network of the psoriasis animal model applied with Chinese herbal compound.The 12 samples of blood serum were taken from two groups above(six Kunming mice,six C57mice,male and female was equal).The level of IL-1R, IL-2,IL-5,IL-6,IL-10,TNF-a in peripheral blood of six groups had no difference,but the level of IFN-γ,GM-CSF,IL-17,IL-4 had statistical difference,and its level of some doses groups of traditional Chinese medicine were elevated in different degree.
The research shows that Chinese herbal compound with the action of clearing heat and removing blood stasis treating the blood-heat syndrome of psoriasis in clinic is effective and safe,and the therapy is simple accurate. The experiment shows that the compound can evidently resist against the vaginal epithelium mitosis,and inhibit epidermal cell proliferation;secondly the doses of IFN-γ,GM-CSF,IL-17,IL-4 in clearing heat and removing blood stasis treatment groups of mice serum increase at various levels.Suggesting that the principles of the therapy may be not the simple increase and decrease of the simple cell factor,but the result of multiple cytokines interaction.Anyway the mechanism need further study,and the dosage form needs be improving.
在总结前从经验的基础上,我们结合岭南气候湿热多变特点,从瘀热互结的角度出发,对中医“从血”论治银屑病进行了多方面的探讨,认为银屑病系血热内蕴,郁久化毒,以致血热毒邪外壅肌肤而发病,热毒入里,耗伤津液,瘀滞气血,其发展变化的不同阶段病理变化虽各有不同,但均有热、瘀的病理特点,瘀热互结贯穿疾病的全过程。据此以《伤寒论》太阳病蓄血证瘀热互结证治为指导,制定清热祛瘀中药复方,通过临床和实验研究探讨其治疗银屑病的疗效及其作用机理。
全文包括文献综述和研究报告两部分。
文献综述包括两部分。第一部分综述中医药治疗银屑病的临床与研究进展,包括银屑病的历史沿革,近代及现代医家对银屑病病因病机的认识,以及中医内外治方法及近年的临床及实验研究进展。第二部分综述了银屑病的西医临床与研究进展,由于本病的病因及发病机制均未明确,临床缺乏有效的治愈手段,故本病一直是皮肤科领域内的研究重点及难点,至今尚未有肯定结论,综述包括了流行病学、病因及发病机制、治疗等方面。
研究报告包括临床研究和实验研究两部分。
临床研究通过清热祛瘀复方治疗银屑病血热证的临床验证,探讨中药复方治疗银屑病血热证的临床疗效,由广州中医药大学第一附属医院皮肤科临床研究的完成。
在清热祛瘀复方治疗银屑病血热证临床验证中,共选取银屑病血热证78例,其中治疗组40例,雷公藤多甙片对照组38例,两组性别、年龄、病程、皮损形态、治疗前PASI评分、中医临床症候症状评分差异无统计学意义(P＞0.05),具有可比性。
结果显示:治疗组及对照组治疗前后PASI评分比较具有显著性差异(P＜0.05),治疗后两组PASI评分比较无统计学意义(P＞0.05)。两组总体疗效经经卡方检验比较差异无统计学意义(P＞0.05);说明清热祛瘀复方与雷公藤多甙片总体疗效相当。清热祛瘀复方明显改善患者皮肤瘙痒、心烦、口渴、便秘、尿黄、舌象、脉象等中医临床症候。结果表明中药复方治疗寻常型银屑病血热证有较好疗效。尤其对心烦、口渴、大小便等中医临床症状均具有良好疗效。
实验研究包括三部分:
实验研究一:利用雌激素期增生的小鼠阴道上皮模型研究清热祛瘀复方抑制增殖作用。昆明种雌性小鼠随机分为6组:中药复方小、中、大剂量组(1、2、3组)、雷公藤多甙组(4组)、雷公藤多甙+中药组(5组)、阴性对照组(6组)。在此项实验中,阴性对照组与雷公藤对甙组比较有极显著差异(P＜0.05),阴性对照组与小剂量中药组、大剂量中药组及雷公藤对甙+中药组比较也有显著差异(P＜0.05)。中药各组与雷公藤多甙组比较发现,中药中剂量组与雷公藤多甙组比较有显著差异(P＜0.05),中药小、大剂量组,及雷公藤多甙+中药组与雷公藤多甙组比较差异无统计学意义(P＞0.05)。
实验研究二:利用小鼠尾鳞片表皮模型研究清热祛瘀复方促进分化的作用,C57小鼠分组同上,在此项实验中,大中药组与阴性对照组相比有统计学意义(P＜0.05),但并没有促进小鼠尾部鳞片表皮颗粒层的形成。雷公藤多甙组与阴性对照组相比无统计学意义(P＞0.05)。并且用药的5组都没有显著促进小鼠尾部鳞片表皮颗粒层的形成。
实验三:利用CBA技术观察中药复方对银屑病动物模型细胞因子网络的影响。上述二组小鼠各取12份血清样本(昆明种每组取6只,C57小鼠每组取6只,♀♂各半)。6组外周血中IL-1R、IL-2、IL-5、IL-6、IL-10、TNF-a的水平并无统计学意义。而不同组别小鼠血清中IFN-γ、GM-CSF、IL-17、IL-4水平有统计学意义,且在某些剂量中药用药组都有不同程度的升高。
研究表明祛清热祛瘀复方临床治疗银屑病血热证安全有效,简便易行;该药具有明显抑制实验小鼠阴道上皮细胞增生过快,提示该药能抑制银屑病表皮增生过快;其次,清热祛瘀复方能提高小鼠血清中IFN-γ、GM-CSF、IL-17、IL-4水平,提示该药治疗银屑病可能是多种细胞因子相互作用的结果,而不是单个细胞因子的简单升降所引起的,但其机理仍有待进一步研究,且剂型亦有待改善。
Psoriasis,which is commonly called "niupixuan" and called "baibi" in traditional Chinese medicine,is the common chronic recurrent inflammatory dermatoses,and its skin lesions appearance is red maculopapule covered multilayer argentate scale.Its prevalence of male is higher than female,its prevalence in city is higher than in country,and its prevalence in north is higher than in south.The prevalence in nature population is about 0.1-3%, which has obvious seasonality.The prevalence in the white race is highest and lowest in melanian and modera in xanthoderm.It is believed in our Chinese medicine that the occurrence of psoriasis is related with blood heat,blood deficiency and blood stasis which caused by invasion of exogenous evil, internal injury caused by excess of seven emotions,estrangement of spleen and stomach and so on.Meanwhile it is believed in western medicine that the main reasons or inducement of its occurrence and development are genetic factor, infection,dysmetabolism,endocrine secretion factor,immunity factor,spirit factor and so on.
On the basis of before experience summary,considered the characteristics of lingnan climate,from the angle of stagnation of blood stasis and heat, exploring the "from heat" treatment of psoriasis in many ways,it is believed that psoriasis is caused by intrinsic blood heat which turns into toxic because of long time stagnation,and its leads to the toxic evil of blood heat outward to skin and muscle and causes the disease.Heat toxic invading inward which leads to depletion of body fluid and stagnation of Qi and blood is the pathological change of different stage of psoriasis developing and changing, though it is different,the pathological characteristics has heat and blood stasis,and stagnation of blood stasis and heat breaks through the wholes process.Because of that,we followed the guidance of the principle of treating stagnation of blood stasis and heat of Taiyang syndrome of blood stasis of《Treatise on Cold-induced Febride Diseases》,worked out the Chinese herbal compound which has the action of clearing heat and removing blood stasis,and explored the curative effect and mechanism of action of treating psoriasis by the clinical and experimental study.
This article is divided into two parts.One is literature review and the other is research report.
Literature review includes two parts.The first one,Traditional Chinese clinic and research development on the psoriasis,includes its successive changes,the opinions of neoteric doctors on its pathogenesis and medical and surgical treatment.The second one is modern clinic and research development on the psoriasis.It gains special concerns of the academic circles' owing to its unknown etiological factors and pathogenesis.Besides,it is scarce of effective therapeutic tools.Considerable research has been performed on epidemiology,etiological factors,pathogenesis,and therapy in recent years.
The research report includes two parts.One is about clinical research, and the other is about experimental one.
Clinical verification on blood-heat syndrome of psoriasis treated by Chinese herbal compound with the action of clearing heat and removing blood stasis was performed and clinical effect was explored.And the clinical research was completed by departmrnt of dermatology of the first affiliated hospital of Guangzhou university of traditional Chinese medicine.
In clinical verification on blood-heat syndrome of psoriasis applyed with Chinese herbal compound with the action of clearing heat and removing blood stasis,78 cases with blood-heat syndrome were selected and 40 cases applied with Chinese herbal as treatment group and 38 cases applied with Tripterygium Wilfordii tablet for controlled group.The two groups had comparability because there were no significant deviations in the sex,age,course of disease,shape of skin destruction,PASI score before treatment,syndromes score between them.
Results showed that there was significant difference of PASI score before and after the treatment in both groups(P＜0.01).There was no significant difference of PASI score after the treatment in both group(P＞0.05).And there was no significant difference of general efficacy between the two groups(P＞0.05),which indicated that the both are effective.Chinese herbal compound with the action of clearing heat and removing blood stasis could improve clinical symptoms of Chinese medicine such as itch of skin,upset, thirsty,constipation,yellow urine,tongue picture,pulse demonstration and so on.And the results showed that there was better efficacy using Chinese herbal compound with the action of clearing heat and removing blood stasis treating ordinary blood heat syndrome of psoriasis,especially in clinical symptoms of Chinese medicine such as upset,thirsty,urine and stool and so on.
Experimental research includes three parts:
Experimental researchⅠ:The model of proliferative vaginal epithelial cells of mice in estrogen cycle was used to study the prohibition efficacy of Chinese herbal compound with the action of clearing heat and removing blood stasis.Kunming female mice was randomly divided into six group:small,medium and large doses groups of Chinese herbal(groupl,2,3),tripterygium glycosides group(group4),tripterygium glycosides plus Chinese medicine group (group5) and negative control group(group6).In the experimental research, there was statistical difference between negative control group and tripterygium glycosides group(P＜0.05),between negative control group and small doses group of traditional Chinese medicine,large doses group of traditional Chinese medicine,and tripterygium glycosides plus Chinese medicine group.It was found that there was statistical difference between medium doses group of traditional Chinese medicine and tripterygium glycosides group(P＜0.05),and there was no differencein tripterygium glycosides group compared with small doses group of traditional Chinese medicine,large doses group of traditional Chinese medicine,and tripterygium glycosides plus Chinese medicine group(P＞0.05).
Experimental researchⅡ:The model of the scale epidermis cells of mice tail was used to study the promoting differentiation efficacy of Chinese herbal compound with the action of clearing heat and removing blood stasis.C57 mice Groups were divided as above.In the experimental research,there was statistical difference between negative control group and large doses group of traditional Chinese medicine(P＜0.05),but it dose not promote the formation of the scale epidermis cells of the tail.there was no difference between tripterygium glycosides group and negative control group(P＞0.05).the promoting function of formation of the scale epidermis cells of the tail was not obvious in five groups with drugs.
Experimental researchⅢ:CBA technique was used to observe the influence on cytokine network of the psoriasis animal model applied with Chinese herbal compound.The 12 samples of blood serum were taken from two groups above(six Kunming mice,six C57mice,male and female was equal).The level of IL-1R, IL-2,IL-5,IL-6,IL-10,TNF-a in peripheral blood of six groups had no difference,but the level of IFN-γ,GM-CSF,IL-17,IL-4 had statistical difference,and its level of some doses groups of traditional Chinese medicine were elevated in different degree.
The research shows that Chinese herbal compound with the action of clearing heat and removing blood stasis treating the blood-heat syndrome of psoriasis in clinic is effective and safe,and the therapy is simple accurate. The experiment shows that the compound can evidently resist against the vaginal epithelium mitosis,and inhibit epidermal cell proliferation;secondly the doses of IFN-γ,GM-CSF,IL-17,IL-4 in clearing heat and removing blood stasis treatment groups of mice serum increase at various levels.Suggesting that the principles of the therapy may be not the simple increase and decrease of the simple cell factor,but the result of multiple cytokines interaction.Anyway the mechanism need further study,and the dosage form needs be improving.
引文
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