基于p38MAPK/NF-κB信号通路探讨外用应急软膏治疗银屑病的机制研究

Study on the mechanism of Waiyong Yingji ointment in the treatment of psoriasis:#br#based on p38MAPK/NF-κB signaling pathway

目的探究外用应急软膏对咪喹莫特诱导的寻常型银屑病小鼠皮损组织中白介素(interleukin,IL)-17a、肿瘤坏死因子(tumor necrosis factor,TNF)-α、干扰素(interferon,IFN)-γ及p38丝裂原活化蛋白激酶(p38 mitogen-activated protein kinase,p38MAPK)/核因子(nuclear factor,NF)-κB通路相关蛋白表达水平的影响,并探讨其作用机制。方法选取30只6~8周龄SPF级雄性BALB/c小鼠,随机分为空白组、模型组和外用应急软膏组,每组10只。模型组和外用应急软膏组分别用咪喹莫特诱导银屑病小鼠模型,外用应急软膏组在造模同时外涂外用应急软膏治疗,共7 d。7 d后取各组小鼠皮损组织,通过酶联免疫吸附试验、免疫印迹法及免疫组化检测相关蛋白表达。结果与模型组相比,外用应急软膏组小鼠皮损组织中IL-17a、TNF-α及IFN-γ炎症因子的表达水平明显降低(P<0.05);同时可显著降低皮损组织中p-p38/p38、p-IκBα/IκBα及p-p65/甘油醛-3-磷酸脱氢酶蛋白表达比值(P<0.05),且p-P38MAPK、p-p65及p-IκBα阳性表达水平显著降低(P<0.05)。结论外用应急软膏对咪喹莫特诱导的银屑病小鼠具有治疗作用,可能是通过抑制p38MAPK/NF-κB信号通路的表达抑制IL-17a、TNF-α及IFN-γ等相关细胞因子的分泌,从而发挥抗炎作用,改善病情。

Objective To explore the effect of WaiYong YingJi ointment on interleukin(IL)-17a,tumor necrosis factor(TNF)-α,interferon(IFN)-γand p38 mitogen-activated protein kinase(p38MAPK)/nuclear factor(NF)-κB pathway related protein expression level in the skin lesions of mice with imiquimod-induced psoriasis vulgaris and its mechanism.Methods Thirty male BALB/c mice aged 6 to 8 weeks were randomly divided into blank group,model group and Waiyong Yingji ointment group,and 10 cases in each group.The model group and Waiyong Yingji ointment group were treated with imiquimod to induce psoriasis,and the Waiyong Yingji ointment group was treated with Waiyong Yingji ointment at the same time as the model for 7 days.Seven days later,the skin tissue of mice in each group was taken,and enzyme-linked immunosorbent assay,western blotting and immunohistochemistry were used to detect the expression of related proteins.Results Compared with model group,the levels of inflammatory cytokines IL-17a,TNF-αand IFN-γin Waiyong Yingji immunoointment group were significantly decreased(P<0.05).The ratios of p-p38/p38,p-IκBα/IκBαand p-p65/glyceraldehyde-3-phosphate dehydrogenase in skin lesions were significantly decreased(P<0.05),and the positive expression levels of p-p38MAPK,p-p65 and p-IκBαwere significantly decreased(P<0.05).Conclusion Waiyong Yingji ointment has therapeutic effect on imiquimote-induced psoriasis mice,which may play an anti-inflammatory role by inhibiting the expression of p38MAPK/NF-κB signaling pathway and the secretion of IL-17a,TNF-α,IFN-γand other related cytokines,so as to improve psoriasis.