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丹槐银屑浓缩丸对豚鼠银屑病样模型病理形态及组织TNF-α,TGF-β1的影响

The Empirical Study of Dhyxnsw’s Effect on the Pathological Morphology and TNF-α, TGF-β1 of Psoriasiform-Model’s Guinea Pig

【作者】 陶以成

【导师】 王学军;

【作者基本信息】 黑龙江中医药大学 , 中西医结合临床, 2010, 博士

【摘要】 银屑病是一种常见并易复发的慢性炎症性疾病,病因及发病机制尚未完全明了。现代研究证明与遗传缺陷、免疫功能障碍、神经介质的变化、细胞增殖与凋亡异常、微循环障碍、代谢和内分泌紊乱、神经精神功能障碍等多种因素有关,是遗传因素与环境因素等多种因素相互作用的多基因遗传病。目前西药治疗银屑病疗效可靠但毒副作用较大,且停药易复发。中医药治疗银屑病疗效可靠,毒副作用小,已成为现在临床和科研的热点。银屑病是多基因遗传背景下的机体免疫失常的疾病,免疫介导是疾病的主要发生机制。在病理生理上表现为角质形成细胞的在免疫因子的作用或介导下过度角化和角化不全,基底层迂曲变形,棘层增厚,颗粒层变薄或消失,真皮浅层毛细血管增生,炎性细胞浸润等。临床上丹槐银屑浓缩丸用于血热型银屑病(寻常型)的治疗,疗效可靠。本课题的目的是研究中药丹槐银屑浓缩丸对豚鼠银屑病样模型的表皮病理变化及银屑病相关免疫因子的影响。我们通过制备豚鼠银屑病样模型,设空白组、模型组、西药和成药对照组以及高、中、低三个剂量组,考察丹槐银屑浓缩丸对银屑病过度角化和角化不全抑制作用和对银屑病相关免疫因子的调节作用以及这些作用与剂量的依赖关系。结果显示丹槐银屑浓缩丸对豚鼠银屑病样模型有明显的治疗作用。本实验显示丹槐银屑浓缩丸中、低剂量组疗效优于成药对照组而与西药对照组相当。由此推断,丹槐银屑浓缩丸中、低剂量可能通过抑制表皮细胞增殖与促进其分化,抑制细胞炎症因子,参与抗炎与免疫调节过程来发挥治疗作用的。而高剂量作用却不明显,其机理有待进一步研究。该研究的成果为丹槐银屑浓缩丸治疗银屑病的临床疗效作了有力的验证和为丹槐银屑浓缩丸治疗银屑病临床方案的合理化和优化提供了有力的实验依据。

【Abstract】 Psoriasis is a chronic inflammatory dermatosis characterized by erythema and generous scales. As a common disease throughout the world it does great harm to patients’physical and mental health. The aetiology of psoriasis is known incompletely and the curative effect is not very satisfatory. But modern researches have demonstrate that Psoriasis has greatly something to do with heredity, immunologic function dysfunction, infection, inflammation, neuromediator, endocrine, cell proliferation and apoptosis, microcirculation disorder, metabolism, nerve and psyche ,and so on. Psoriasis is the interactive result of genetic factor and environment factor. So far western medicine have certain curative efect on psoriasis but not can do without toxic and side-effect, furthermore, relatpseing is frequent after drug withdrawal. So herb therapy on psoriasis is a prevalence in china and in the world because of the true cure and lower toxic and lower side-effect than western medicine.Psoriasis is a disease of immune disturbance under polygenic inheritance. The fundamental mechanism is the immune incorreted interference. Modern researches have established hyperkeratinization and parakeratosis of keratinocytes and the hyperplasia of the capillary vessel in the dermis as the fundamental pathological changes. Clinically, we apply DHYXNSW to treating Xuerexing-psoriasis (psoriasis vulgaris),and the effect is significant. This study is aimed to observe the effet of DHYXNSW on pathological changes and immune factors associated with psoriasis of guinea pig model of psoriasis-like skin. Through establishing two control groups of Methotrexate and FFQDJN and establishing high, medium and low dose groups of DHYXNSW to treating guinea pig of psoriasis-like model, we investigate the inhibition of psoriatic hyperkeratosis and parakeratosis, and mediating of immune factors of guinea pig of psoriasis-like model and their dose-dependent effects. The results show that DHYXNSW have significant therapeutic effect on psoriasis-like model of guinea pig, and the effects are not significantly correlated with the dose. This study demonstrates that the therapeutic effects of medium, low dose group of DHYXNSW are better than the FfqdJN group but are as good as the Western medicine group in inhibiting the epidermal cell proliferation and promoting their differentiation,inhibiting cytokine involved in inflammatory and immune processes. Effect at high doses is close to FfqdJN group but no better than medium and low dose group, the mechanism needs further study. The study’s results of DHYXNSW efffect of the treatment of psoriasis-like model provides with a powerful experimental evidence to the treatment of psoriasis in clinic and play a significantcant role in the rationalization and optimization of clinical programs.

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