局部外用CKLF1拮抗肽C19在小鼠特应性皮炎的治疗作用

摘要

目的 探讨趋化素样因子1(CKLFl)拮抗肽C19局部外用对小鼠特应性皮炎(AD)模型的作用,并探索 C19浓度与小鼠AD治疗效果的关系.方法 用卵清蛋白(OVA)经皮致敏BALB/c小鼠腹部,建立小鼠AD模型.将55只小鼠按照随机数字表法分成空白对照组、皮炎组、治疗组a、治疗组b和治疗组c,每组各11只.其中空白对照组和皮炎组给予0.9％氯化钠溶液局部外用治疗,治疗组a、b、c三组则分别给予0.1 μg/ml、1.0 μg/ml、10.0 μg/ml浓度的C19局部外用治疗.治疗隔日1次,共4次,治疗结束后,观察并记录各组小鼠皮损改变;收集小鼠皮损及血清,观察其組织病理学改变、组织中相关炎症因子及血清总IgE水平.结果 ①与空白对照组相比,皮炎组和治疗组小鼠局部皮肤出现明显的水肿、红斑、渗出、皮屑、结痂等皮疹表现,建模成功.②治疗结束后,经C19局部外用治疗后,AD小鼠局部皮肤外观及皮损组织病理学炎症减轻;与皮炎组相比,组织匀浆炎症因子IL-4和IL-5均在治疗组c中显著降低(P＜0.05),而治疗组a、b与皮炎组相比差异无统计学意义(P＞0.05);与皮炎组相比,组织匀浆炎症因子IL-13和嗜酸性粒细胞趋化因子(Eotaxin)在治疗组a、b、c组中均显著下降,差异具有统计学意义(P＜0.05),而IL-13和Eotaxin在治疗组a、b、c三组中差异均无统计学意义(P＞0.05).结论 CKLF1拮抗肽C19在小鼠AD模型中可以经皮肤吸收发挥治疗作用,对于血清IgE及组织匀浆IL-4、IL-5,高浓度C19对AD的作用效果优于低浓度C19;对于组织匀浆IL-13和Eotaxin,C19对AD的作用效果无明显浓度依赖性.%Objective Through the external using chemokine- like factor 1 (CKLF1) antagonism peptides C19 topical administration, to investigate its function in the mouse model with atopic dermatitis. And to analyze the relationship between C19 concentration and the therapeutic effect of atopic dermatitis in mice. Methods The mouse models of atopic dermatitis were established by sensitizating with ovalbumin (OVA) through the skin.55 BALB/c mice were randomly divided into atopic dermatitis (AD) group, control group, prevention group and treatment group a, b and c, 11 mice in each group. The control group and dermatitis group were treated with topical 0.9％ sodium chloride treatment. The treatment groups (a, b and c) were treated with C19 topical application of 0.1 μg/ml, 1.0 μg/ml and 10.0 μg/ml, respectively. At the end of treatment, the lesions of mice in each group were observed and recorded. The lesions and serum of mice were collected and the histopathological changes, the related inflammatory factors and the serum total IgE level were observed. Results ①Compared with the blank control group,dermatitis group and the treatment group showed obvious edema, erythema, exudation, dander, scab and other skin rash on the local skin of the mice. The modeling was successful.②After treatment, local skin appearance and histopathological inflammation of AD mice were alleviated after local topical treatment with C19. Compared with dermatitis group, inflammatory factors IL-4 and IL-5 in tissue homogenate were significantly decreased in treatment group c (P ＜0.05), while there was no significant difference between the treated group and the dermatitis group (P ＞0.05). Compared with the dermatitis group, the levels of inflammatory cytokines IL (P ＜0.05), while IL- 13 and Eotaxin decreased significantly in treatment group a, b and c, and the difference was statistically significant. There was no significant difference in a, b and c groups (P ＞0.05). Conclusion CKLF1 antagonist peptide C19 can play a therapeutic role in skin- specific absorption in mouse- specific dermatitis model. The effect of high concentration C19 in serum IgE and tissue homogenate IL-4 and IL-5 is better than that of low concentration C19. In Eotaxin and IL- 13, its therapeutic effect has no concentration dependence.