麻黄连轺赤小豆汤对特应性皮炎模型小鼠皮肤屏障功能的影响

Effects of Mahuang Lianzhi Chixiaodou Decoction on Skin Barrier Function in Atopic Dermatitis Model Mice

目的:探讨麻黄连轺赤小豆汤对不同时期特应性皮炎(atopic dermatitis, AD)模型小鼠皮肤屏障功能的影响。方法:采用随机数字表法将120只雄性BALB/c小鼠随机分为正常组、模型组、糠酸莫米松组和麻黄连轺赤小豆汤组。除正常组外,其余组小鼠采用2,4-二硝基氟苯(2,4-dinitrofluorobenzene, DNFB)反复刺激皮肤建立AD动物模型。于实验第4、18、32、39天4个时间点分别进行药物干预,麻黄连轺赤小豆汤组灌胃给予麻黄连轺赤小豆汤(11.98 g·kg^(-1)·d^(-1)),每日2次;糠酸莫米松组于小鼠皮损处均匀涂抹适量0.1%糠酸莫米松凝胶,每日2次;正常组和模型组给予等量常温蒸馏水灌胃,每日2次;每个时间点连续干预7 d。于第11、25、39、46天4个时间点分别考察各组小鼠皮损评分、皮肤组织病理学、皮肤酸碱度(pondus hydrogenii, pH)及经皮水分散失(trans epidermal water loss, TEWL)情况。结果:与正常组相比,AD模型组小鼠整个观察周期各时间点皮损评分、TEWL值均明显升高(P<0.01);第11、25、39天3个观测点pH值均明显升高(P<0.01)。与模型组相比,麻黄连轺赤小豆汤组小鼠第39、46天两个时间点TEWL值显著下降(P<0.01);第11、25、39天3个观测点皮肤pH值均明显降低(P<0.01)。HE染色发现AD模型组小鼠四个观察点皮肤组织表现依次为:表皮增厚,以棘细胞层增厚为主→表皮增厚,棘细胞层增生变厚→表皮增厚,棘细胞层显著增厚→表皮增厚减轻,棘细胞层增生减轻等;而麻黄连轺赤小豆汤可明显改善模型小鼠皮肤病理改变。皮损评分、TEWL值、pH值的相关分析发现,皮损评分、pH值、TEWL值三者呈正相关关系,可共同加重皮肤屏障功能障碍。结论:麻黄连轺赤小豆汤可有效改善AD模型小鼠皮肤屏障功能,以亚急性期治疗效果最佳。

Objective: To investigate the effect of Mahuang Lianyao Chixiaodou Decoction on the skin barrier function of atopic dermatitis(AD) model mice at different stages.Methods: 120 male BALB/c mice were randomly divided into normal group, model group, mometasone furoate gel group, and Mahuang Lianyao Chixiaodou Decoction group(11.98 g/kg·d^(-1)) by random number table method.Except for the normal group, mice in other groups were repeatedly stimulated with 2,4-dinitrofluorobenzene(DNFB) to establish AD animal models.Drug intervention was carried out on the 4 th, 18 th, 32 nd, and 39 th days of the experiment, and the Mahuang Lianyao Chixiaodou Decoction group was given Mahuang Lianyao Chixiaodou Decoction by gavage, twice a day.In the mometasone furoate gel group, an appropriate amount of 0.1% mometasone furoate gel was evenly applied to the skin lesions of the mice, once a day.The normal group and the model group were given the same amount of distilled water at room temperature, twice a day, while each time point for 7 consecutive days of intervention.On the 11 th, 25 th, 39 th, and 46 th days after modeling, the skin lesion scores, skin histopathology, pondus hydrogenii(pH),and Trans Epidermal Water Loss(TEWL) were observed in each group.Results: Compared with the normal group, the skin lesion score and TEWL value of the mice in the AD model group were significantly increased at each time point throughout the observation period(P<0.01).The pH values of the three observation points on the 11 th, 25 th, and 39 th days were significantly increased(P<0.01).Compared with the model group, the TEWL values of the mice in the Mahuang Lianyao Chixiaodou Decoction group decreased significantly at the 39 th and 46 th days(P<0.01),and on the 11 th, 25 th, and 39 th days, the pH of the skin decreased significantly(P<0.01).HE staining showed that the skin tissue manifestations of the four observation points in the AD model group were as follows: epidermal thickening, mainly acanthocyte layer thickening→epidermis thickening, acanthocyte layer hyperplasia and thickening→epidermis thickening, acanthocyte layer significantly Thickening→Reduced epidermal thickening, reduced acanthocyte layer hyperplasia, etc.However, the Mahuang Lianyao Chixiaodou Decoction group could significantly improve the skin pathological changes of the model mice.The correlation analysis of skin lesion score, TEWL,and pH found that the skin lesion score, pH value, and TEWL value were positively correlated, which could jointly aggravate skin barrier dysfunction.Conclusion: Mahuang Lianyao Chixiaodou Decoction can effectively improve the skin lesions of AD model mice, with the best therapeutic effect in the subacute stage.