Goknur Demiran, Rukiye Yasak Guner, Mustafa Ozkara, Mustafa Tosun, Melih Akyol
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引用次数: 0
摘要
目的:考虑到两种疾病之间共同的免疫致病机制,本研究的目的是评估用于治疗多发性硬化症(MS)的药物系统性醋酸格拉替默(GA)在吡喹莫德诱导的银屑病小鼠模型中的治疗潜力。材料与方法:54只成年雌性BALB/c小鼠(16 ~ 18周龄)分为9组,每组6只。8组均采用5%咪喹莫特乳膏连续7 d造银屑病样模型。全身治疗包括甲氨蝶呤(2mg /kg/周)、生理盐水(1ml /kg/天)和GA,剂量从50到100微克不等,在诱导期或诱导期后皮下给药。采用改良的银屑病面积和严重程度指数(mPASI)评估临床严重程度,同时进行组织病理学和免疫组织化学分析以评估炎症和细胞因子表达,重点是TNF-α, IL-1β和IL-17。结果:银屑病治疗组mPASI评分最高,而健康对照组和50 mcg GA治疗小鼠,特别是诱导后的mPASI评分最低。结论:在试验剂量中,模型诱导后给予50mcg GA在降低临床严重程度和炎症细胞因子表达方面最有效。这些发现表明GA是一种很有前途的银屑病全身治疗药物。
Therapeutic effect of systemic use of glatiramer acetate in imiquimod-induced mouse psoriasis model.
Purpose: The aim of this study is to evaluate the therapeutic potential of systemic glatiramer acetate (GA), a drug used in the treatment of multiple sclerosis (MS), in an imiquimod-induced psoriasis mouse model, given the common immunopathogenic mechanisms between the two diseases.
Materials and methods: Fifty-four adult female BALB/c mice (16-18 weeks old) were divided into nine groups (6 mice each). A psoriasis-like model was induced in eight groups by application of 5% imiquimod cream for seven days. Systemic treatments included methotrexate (2 mg/kg/week), saline (1 mL/kg/day) and GA at doses ranging from 50 to 100 mcg, administered subcutaneously either during or after the induction phase. Clinical severity was assessed using the modified Psoriasis Area and Severity Index (mPASI), while histopathological and immunohistochemical analyses were performed to assess inflammation and cytokine expression, focusing on TNF-α, IL-1β and IL-17.
Results: The highest mPASI scores were observed in the untreated psoriasis group, whereas the healthy control and mice treated with 50 mcg GA, especially after induction, showed the lowest scores. Statistically significant improvements in histopathological scores were observed (p < 0.05). GA treatment at 50 mcg resulted in the most favourable cytokine profile, with TNF-α and IL-17 levels comparable to the healthy group and a similar trend observed for IL-1β expression.
Conclusions: Among the doses tested, 50 mcg GA administered after model induction was the most effective in reducing clinical severity and inflammatory cytokine expression. These findings suggest that GA is a promising systemic therapeutic agent for psoriasis.
期刊介绍:
Cutaneous and Ocular Toxicology is an international, peer-reviewed journal that covers all types of harm to cutaneous and ocular systems. Areas of particular interest include pharmaceutical and medical products; consumer, personal care, and household products; and issues in environmental and occupational exposures.
In addition to original research papers, reviews and short communications are invited, as well as concise, relevant, and critical reviews of topics of contemporary significance.