氨基酮戊酸甲酯联合自然光照对咪喹莫特诱导小鼠银屑病样皮损模型治疗机制初探

Study on the treatment mechanism of methyl aminolevulinate combined with natural light for imiquimod induced psoriasis in mice

目的研究氨基酮戊酸甲酯(methyl aminolevulinate,MAL)联合自然光照对咪喹莫特诱导小鼠银屑病样皮损模型治疗效果及血清干扰素(interferon,IFN)-γ、白介素(interleukin,IL)-17A及IL-4等细胞因子表达水平的影响,初步探讨MAL联合自然光照治疗寻常型银屑病的免疫机制。方法将30只BALB/c雄性小鼠随机平均分为正常对照组、银屑病模型组及MAL高、中、低剂量组,每组6只。采用咪喹莫特乳膏外涂表皮的方法制备银屑病模型。参考银屑病皮损严重程度指数(psoriasis skin lesion severity index,PASI)评分观察银屑病样小鼠模型皮损动态变化;光镜观察皮损组织病理变化;采用酶联免疫法(enzyme linked immunosorbent assay,ELISA)检测小鼠血清中细胞因子含量。结果 MAL联合自然光照各组小鼠皮肤红斑程度、鳞屑厚度、皮肤增厚均小于同期的模型组改变(P<0.05)。苏木精-伊红染色显示,MAL各组小鼠皮肤表皮层较平整,角化不全的细胞明显减少,表皮层厚度低于模型组(P<0.01)。血清ELISA检测显示,MAL组小鼠血清IFN-γ及IL-17A表达较模型组降低(P<0.01),IL-4的表达增高(P<0.01)。结论 MAL联合自然光照可抑制咪喹莫特诱导的银屑病样炎症爆发的强度及银屑病样皮损的形成,通过降低辅助性T细胞(T helper cells,Th)1、Th17相关细胞因子IFN-γ、IL-17A的表达及增加Th2相关细胞因子IL-4的表达,对Th1/Th2 /Th17细胞的分化进行调节,发挥抗炎作用。

Objective To study the effect of methyl aminolevulinate (MAL) combined with natural light on the treatment of imiquimod induced psoriasis in mice and the expression levels of cytokines such as IFN-γ,IL-17A and IL-4,and to preliminarily explore the immune mechanism of MAL in the treatment of psoriasis vulgaris.Methods A total of 30 male BALB/c mice were randomly divided into normal control group,psoriasis model group and MAL high,medium and low dose group,each group with 6 cases.The psoriatic model was made according to applying imiquimod cream.The psoriasis skin lesion severity index (PASI) score was used to observe the dynamic changes of skin lesions in the psoriasis mouse model.Pathological changes of skin lesions were observed by light microscope.The cytokine content in serum of mice was detected by enzyme linked immunosorbent assa (ELISA).Results The degree of skin erythema,scale thickness and skin thickening in each group were smaller than those in the model group (P<0.05).Hematoxylin-eosin staining showed that the skin epidermis of the mice was relatively flat,the keratinocytes were significantly reduced,and the epidermis thickness was lower than that of the model group (P<0.01).Serum ELISA showed that the expression of IFN-γ and IL-17A in the serum of methyl aminolevulinate group was lower than that of the model group (P<0.01),while the expression of IL-4 was higher (P<0.01).Conclusion Methyl aminolevulinate combined with natural light can inhibit the intensity of imiquimod induced psoriasis like inflammation outbreak and the formation of psoriasis like skin lesions,and regulate the differentiation of Th1/Th2/Th17 cells by reducing the expression of IFN-γ and IL-17A related cytokines and increasing the expression of IL-4 related cytokines of Th2.