基于P38MAPK信号通路探讨加味黄连膏对小鼠湿疹模型的影响

Effect of modified huanglian ointment on mouse eczema model based on p38MAPK signal pathway

目的:基于P38MAPK信号通路探讨加味黄连膏对湿疹模型小鼠模型的治疗效果。方法:BALB/c小鼠60只,采用二硝基氯苯(1-chloro-24-dinitrochloro-benzene,DNCB)建立皮肤湿疹模型,随机分为6组,分别为空白对照组、空白基质(模型对照组)、复方醋酸地塞米松软膏(阳性对照组)及高、中、低剂量组(加味黄连膏治疗组),对湿疹部位皮肤连续涂抹给药11d,以HE染色实验结果评价皮肤中炎症细胞浸润情况;Western Blot检测小鼠皮肤组织中p-p38和p38蛋白表达;qRT-PCR法检测皮肤组织中p38MAPKmRNA的表达;ELISA法检测血清中促炎细胞因子白细胞介素-6(interleukin 6,IL-6)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-2(interleukin 2,IL-2)、干扰素(IFN-γ)的水平。结果:药物治疗组与模型对照组相比,小鼠皮肤肿胀明显减轻;与模型对照组比较,血清中细胞因子(IL-2,IL-6,TNF-α和IFN-γ)的水平,加味黄连膏治疗组各组细胞因子水平均低于模型组(P<0.05,P<0.01);且与模型组相比,加味黄连膏治疗组皮肤组织中p-p38MAPK蛋白水平明显下降,p-p38MAPK mRNA表达降低(P<0.05,P<0.01)。结论:加味黄连膏可以通过抑制p38MAPK信号通路的激活,抑制炎症反应,有效治疗皮炎湿疹。

OBJECTIVE To explore the therapeutic effect of Jiawei Huanglian Ointment on mouse model of eczema based on P38 MAPK signal pathway.METHODS Sixty BALB/c mice were randomly divided into 6 groups:blank control group,blank matrix(model control group),compound dexamethasone acetate ointment(positive control group)and high,medium and low dose groups(modified Huanglian ointment treatment group).The skin of eczema site was continuously applied for 11 days.The infiltration of inflammatory cells in the skin was evaluated by HE staining test results.The expression of p-p38 and p38 protein in the skin tissues of mice was detected by Western blot.The expression of p38 MAPK mRNA in the skin tissues was detected by qRT-PCR.The levels of proinflammatory cytokines interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),interleukin-2(IL-2)and interferon(IFN-γ)in the serum were detected by ELISA.RESULTS Compared with the model control group,the skin swelling of the mice in the drug-treated group was significantly reduced.Compared with the model control group,the serum cytokines(IL-2,IL-6,TNF-α and IFN-γ)levels were improved.The levels of cytokines in the Huanglian cream treatment group were lower than those in the model group(P<0.05,P<0.01).Compared with the model group,the p-p38 MAPK protein level and p-p38 MAPKmRNA in the skin tissue of the modified Huanglian cream treatment group were significantly reduced,and the p-p38 MAPK mRNA expression was decreased(P<0.05,P<0.01).CONCLUSION Modified Huanglian ointment can effectively treat dermatitis and eczema by inhibiting the activation of p38 MAPK signaling pathway and inhibiting the inflammatory response.