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首页> 外文期刊>Journal of dermatological science >UVA irradiation following treatment with topical 8-methoxypsoralen improves bleomycin-induced scleroderma in a mouse model, by reducing the collagen content and collagen gene expression levels in the skin
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UVA irradiation following treatment with topical 8-methoxypsoralen improves bleomycin-induced scleroderma in a mouse model, by reducing the collagen content and collagen gene expression levels in the skin

机译：局部用8-甲氧基补骨脂素治疗后的UVA辐射可通过减少皮肤中的胶原蛋白含量和胶原蛋白基因表达水平来改善博莱霉素诱导的硬皮病

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Background: Recent studies have demonstrated that systemic or topical PUVA therapy, i.e., ultraviolet A (UVA) irradiation following treatment with 8-methoxypsoralen (8-MOP), is effective against the sclerotic skin lesions in systemic sclerosis. However, the mechanisms still remain unknown. Objective: To clarify the mechanisms of this therapy, we created a mouse model of bleomycin (BLM) injection-induced scleroderma and evaluated the effects of PUVA on the fibrotic lesions of scleroderma in this mouse model. Methods: BLM was injected subcutaneously once a day into the mice for 24 days. During the injection period, one group of mice was irradiated with UVA following local application of 8-MOP. Control groups were also set up, which were injected with phosphate-buffered saline, instead of BLM. Skin tissue samples examined histopathologically changes, measured of the content of hydroxyproline, and checked for the expression of genes encoding type I collagen, type III collagen, and transforming growth factor-β1 (TGF-β1). Results: The mouse models of scleroderma was found to show an increase in the density of the collagen fibers and thickening of the dermis and increased expressions of type I collagen, type III collagen, and TGF-β1. However, the combination of BLM treatment and topical PUVA treatment mice appeared reduced the dermal thickness and hydroxyproline content, down-regulation of expressions of the type I and type III collagen genes was observed while the expression of the TGF-β1 gene remained unchanged. Conclusion: These results suggest that the effectiveness of topical PUVA therapy is attributable to the down-regulation of the expressions of the collagen genes by this treatment. The results additionally suggest that is not mediated by down-regulated expression of the TGF-β1.
机译：背景：最近的研究表明，全身或局部PUVA疗法，即在用8-甲氧基补骨脂素（8-MOP）治疗后进行紫外线A（UVA）照射，可有效抵抗全身性硬化症中的皮肤硬化病变。但是，机制仍然未知。目的：为阐明该疗法的机制，我们建立了博来霉素（BLM）注射诱导的硬皮病小鼠模型，并评估了PUVA对这种小鼠模型中硬皮病纤维化病变的影响。方法：每天两次向小鼠皮下注射BLM，持续24天。在注射期间，局部应用8-MOP后，用UVA照射一组小鼠。还建立了对照组，给它们注射磷酸盐缓冲盐水代替BLM。皮肤组织样品检查组织病理学变化，测量羟脯氨酸的含量，并检查编码I型胶原，III型胶原和转化生长因子-β1（TGF-β1）的基因的表达。结果：发现硬皮病小鼠模型显示胶原纤维密度增加和真皮增厚，I型胶原，III型胶原和TGF-β1的表达增加。然而，BLM治疗和局部PUVA治疗小鼠的组合出现了真皮厚度和羟脯氨酸含量的降低，观察到I型和III型胶原基因表达的下调，而TGF-β1基因的表达保持不变。结论：这些结果表明局部PUVA疗法的有效性归因于这种疗法对胶原基因表达的下调。该结果另外表明，这不是由TGF-β1的表达下调介导的。

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