【作者】 郝平生；

【导师】 艾儒棣；

【作者基本信息】 成都中医药大学 ， 中医外科学， 2010， 博士

【摘要】 目的：本课题主要通过临床观察寻常型银屑病(进行期血热证)经加味凉血消风散治疗前后PASI评分、中医证候积分、瘙痒程度等变化,初步对此方疗效进行评价,并同时对其安全性进行评价；通过豚鼠银屑病动物模型研究此方对银屑病的作用机制,初步探讨其作用于寻常型银屑病的部分作用机制。方法：临床研究：将60例寻常型银屑病(进行期血热证)患者随机分为加味凉血消风散组30例和复方青黛胶囊组30例,分别给予加味凉血消风散和复方青黛胶囊治疗,4周为一个疗程,连续观察2个疗程,并在治疗结束后判定疗效,同时对试验药物的安全性评价。实验研究：以5%心得安诱导型银屑病动物模型作为研究对象,主要观察实验药物对银屑病样皮损病理改变、TNF-α、PCNA作用及影响进行研究。运用放射免疫法、免疫组化等先进的实验技术和研究手段,从细胞因子、组织蛋白等方面对加味凉血消风散治疗血热证进行期寻常型银屑病的机制进行了探讨。结果：临床观察结果显示：加味凉血消风散治疗30例血热证进行期寻常型银屑病,2个疗程后,显效22例,有效7例,无效1例,总显效率为73.33%,总有效率为96.67%。经过统计其疗效要略优于复方青黛胶囊组(Z=-2.001,P=0.045<0.05)。本试验加味凉血消风散在临床观察期间未发现任何不良反应。实验研究结果表明：诱导型豚鼠动物模型在造模后与空白组比较均表现出银银屑病典型角化过度、角化不全等病理表现;病变组织中肿瘤坏死因子-α(TNF-α)、增殖细胞核抗原(PCNA)呈现高表达性。经过加味凉血消风散治疗后,其耳部组织的角化程度、炎症反应等病理情况有明显改善,各中药剂量组与模型组相比较抑制角化程度均有统计学意义；高剂量中药组与模型组相比较有明显的抗炎性；总之加味凉血消风散可抑制诱导型银屑病样皮损的病理改变。经中药组及阳性对照药物治疗后实验动物耳组织中的TNF-α的含量与模型组比较有降低趋势,其中MTX对照组与模型组有统计学意义P<0.05,高剂量组与模型组有统计学意义P<0.05,MTX对照组与低剂量组有统计学意义P<0.05。但中药高、中、低剂量之间从图表显示量效有一定的关系,但无统计学差异。经中药组(高、中、低)以及阳性药物对照治疗后实验动物耳组织中PCNA的表达,从图示可见组间有降低趋势,中药高、中、低剂量之间虽图示量效有一定的关系,但无统计学差异。结论：临床试验提示：加味凉血消风散治疗血热证进行期寻常型银屑病有较好的疗效和安全性；动物实验研究提示：加味凉血消风散有较好的抗炎、抑制角质形成细胞角化的作用,通过试验揭示加味凉血消风散可通过抑制TNF-α来达到抗炎、抑制角质形成细胞角化的作用。更多还原

【Abstract】 Objective:The subject of clinical observation, mainly through the blood to heat syndrome of psoriasis vulgaris by Jia Wei Liang Xue Xiao Feng San PASI score before and after treatment, the symptom score, changes in the degree of itching, preliminary evaluation of this side effect, while its safety evaluation; through the guinea pig animal model of psoriasis psoriasis side effect of this mechanism and explore its role in psoriasis vulgaris part of the mechanisms.Methods:Clinical study:60 cases will be carried out phase of blood-heat syndrome in patients with psoriasis vulgaris were randomly divided into flavored Jia Wei Liang Xue Xiao Feng San group of 30 cases and compound Indigo capsule group of 30 patients were given flavored cooling blood and compound Indigo Xiaofengsan capsule treatment,4 weeks for a course of treatment, continuous observation of two courses, and after treatment to determine efficacy, while during the period of the trial in the treatment of drug safety evaluation. Experimental Study:Using generally accepted 5% propranolol-induced animal models of psoriasis as an object of study, the main observation of experimental drugs on the model of lesions, TNF-a, PCNA role and impact of research. The organizational structure of the use ofradioimmunoassay, immunohistochemistry and other advanced experimental techniques and research tools, from the cellular ultrastructure, cytokines, proteins and other aspects of the organization flavored Jia Wei Liang Xue Xiao Feng San period of treatment for abnormal blood heat syndrome the mechanisms of psoriasis are discussed.Results:The clinical observation showed that:Jia Wei Liang Xue Xiao Feng San treated 30 cases of blood-heat syndrome type to view psoriasis, two markedly after treatment in 22 cases, effective in 7 cases, ineffective in 1 case, the total effective rate was 73.33% and the total effective rate of 96.67%. Slightly better than its efficacy through statistical compound Indigo capsule group (Z=-2.001, P=0.045<0.05). This test Modified cooling blood in the clinical observation of Xiaofengsan string not found any adverse reactions. Experimental results show that:induced animal model in guinea pigs after modeling were compared with the control group showed typical hyperkeratosis Bank of psoriasis, and other pathological manifestations of parakeratosis; diseased tissue tumor necrosis factor-α(TNF-α), proliferating cell nuclear antigen (PCNA) showed high expression.After Modified Liangxue Xiaofengsan treatment, the ear level of the organization keratosis, inflammation and other pathological conditions have markedly improved, the medicine dose group compared with the model group were statistically significant degree of inhibition keratosis; high dose of Chinese medicine compared with the model group has obvious anti-inflammatory; short flavored Liangxue Xiaofengsan inhibit psoriasis-like lesions induced by the pathological changes.At the same time by the Chinese group and positive control animals treated ear tissue content of TNF-αcompared with the model group decreased, and MTX control group and model group was statistically significant P<0.05, high dose group and model group statistically significant P<0.05, MTX control group and low dose group was statistically significant P<0.05. But the medicine of high, medium and low dose chart shows the dose from among a certain relationship, but not significantly.The Chinese group (high, medium, low) and positive control animals treated ear tissue expression of PCNA, icons can be seen from the group had a lower Chinese high, medium and low doses of dose-effect between the chart shows there though certain relations, but not significantly.Conclusion:The clinical trials Tip:Modified cooling blood Xiaofengsan period of treatment for psoriasis of blood-heat syndrome has good efficacy and safety; animal research suggests that:Modified cooling blood Xiaofengsan better anti-inflammatory, inhibit keratinocyte The role of keratinization forming cells, through the cooling blood test revealed Xiaofengsan Modified by inhibiting TNF-αto regulate the apoptosis of keratinocytes to achieve anti-inflammatory, inhibit keratinocyte keratosis role.更多还原