异甘草素通过JAK/STAT途径治疗小鼠特应性皮炎的机制研究

Mechanism of Isoliquiritigenin in the Treatment of Atopic Dermatitis in Mice Through JAK-STAT Pathway

目的:探讨异甘草素通过Janus激酶-信号转导和转录激活因子(JAK-STAT)途径治疗小鼠特应性皮炎的作用机制。方法:将60只SPF级雄性C57BL/6小鼠随机分成阴性对照组、模型组、异甘草素低剂量组(50mg/kg)、异甘草素高剂量组(100mg/kg)和阳性对照组(泼尼松龙,10mg/kg),每组12只。除阴性对照组外,其他各组小鼠于背部脱毛区及双耳部涂抹2,4-二硝基氯苯(DNCB)制备特应性皮炎(AD)模型,造模成功后第1天,异甘草素低剂量组、异甘草素高剂量组和阳性对照组小鼠给予相应药物灌胃,阴性对照组和模型组小鼠灌胃等量蒸馏水,每天1次,连续灌胃14d后,对小鼠进行抓挠行为评价和皮炎评分,检测血清中白细胞介素-4(IL-4)、肿瘤坏死因子-α(TNF-α)和免疫球蛋白E(IgE)水平,同时检测小鼠致敏部位皮肤组织中JAK1、JAK3、STAT3和STAT6蛋白水平。结果:阴性对照组小鼠皮肤正常;模型组小鼠皮肤出现不同程度的红斑、干燥、抓痕、表皮糜烂脱落,结痂;异甘草素低、高剂量组症状明显减轻,异甘草素高剂量组疗效明显;阳性对照组疗效较异甘草素高剂量组好。与阴性对照组相比,其余各组小鼠抓挠次数、皮炎评分、IL-4、TNF-α、IgE、JAK1、JAK3、STAT3和STAT6蛋白水平增加(P<0.05);与模型组相比,异甘草素低剂量组、异甘草素高剂量组和阳性对照组小鼠抓挠次数、皮炎评分、IL-4、TNF-α、IgE、JAK1、JAK3、STAT3和STAT6蛋白水平降低,异甘草素各剂量组呈剂量依赖性,但效果不如阳性对照组(P<0.05)。结论:异甘草素对AD模型小鼠皮损有治疗作用,其机制可能与抑制JAK-STAT途径有关。

Objective:To investigate the mechanism of isoliquiritigenin in the treatment of atopic dermatitis in mice through Janus kinase-signal transducer and activator of transcription(JAK-STAT)pathway.Methods:Sixty SPF male C57BL/6 mice were randomly divided into negative control group,model group,isoliquiritigenin low dose group(50 mg/kg),isoliquiritigenin high dose group(100 mg/kg)and positive control group(prednisolone,10 mg/kg),with 12 mice in each group.In addition to the negative control group,2,4-dinitrochlorobenzene(DNCB)was smeared on the back depilated area and ears of mice in other groups to prepare atopic dermatitis(AD)model.On the first day after successful modeling,mice in isoliquiritigenin low dose group,isoliquiritigenin high dose group and positive control group were given corresponding drugs by gavage,while mice in negative control group and model group were given the same amount of distilled water once a day.After 14 consecutive days,the mice were evaluated for scratching behavior and dermatitis score,and serum interleukin-4(IL-4),tumor necrosis factor-α(TNF-α)and immunoglobulin E(IgE)levels,the levels of JAK1,JAK3,STAT3 and STAT6 protein in the skin tissue were detected.Results:The skin of mice in negative control group was normal;the skin of mice in the model group showed varying degrees of erythema,dryness,scratches,epidermal erosion and shedding,and scabs;the symptoms of the isoliquiritigenin low and high dose groups were significantly alleviated,and the isoliquiritigenin high dose group had obvious curative effect;the positive control group has better efficacy than that in the isoliquiritin high dose group.Compared with the negative control group,the number of scratches,dermatitis score,IL-4,TNF-α,IgE,JAK1,JAK3,STAT3 and STAT6 protein in the other groups were increased(P<0.05).Compared with the model group,the number of scratches,dermatitis score,IL-4,TNF-α,IgE,JAK1,JAK3,STAT3 and STAT6 protein in the isoliquiritin low dose group,isoliquiritin high dose group and the positive control group decreased,and the effect in the isoliquiritin dose groups was dose-dependent,but the effect was not as good as the positive control group(P<0.05).Conclusion:Isoliquiritin has therapeutic effect on the skin lesions of AD model mice,and its mechanism may be related to the inhibition of JAK-STAT pathway.