不同证型特应性皮炎患者皮损microRNAs表达谱的研究

Researches on MicroRNAs Expression Profiles in Lesions of Atopic Dermatitis Patients with Different Syndromes

目的探讨特应性皮炎(AD)患者皮损中炎症相关microRNAs及趋化因子的表达水平与其中医证型的关联。方法 AD患者79例辨证分型(湿热内蕴、脾虚湿盛、血虚风燥)后,分别采用qPCR和免疫组化法检测皮损标本中的5个炎症相关microRNAs及趋化因子的表达情况,并对不同证型皮损中microRNAs差异表达的免疫调节作用进行分析。结果湿热内蕴组中miR-21相对表达量上调而miR-125b下降明显,两者与血虚风燥组及正常对照组相比差异均有显著性意义(P<0.01);此时TARC/CCL17表达量较高,阳性颗粒主要分布于基底层和真皮层。脾虚湿盛组中miR-155表达量较高,明显高于其他2组和正常对照组(P<0.01),miR-203虽有所下调,但与其他几组相比差异均不具有统计学意义(P>0.05);此时皮损中表达最高的是CTACK/CCL27分子,散在分布于表皮与真皮,RANTES/CCL5与湿热内蕴组相比亦表达上调。血虚风燥组中miR-146a的表达水平有所上调,与湿热内蕴组及正常对照组相比差异有统计学意义(P<0.01);RANTES/CCL5表达增高,明显高于湿热内蕴组(P<0.01);TARC/CCL17分子与脾虚湿盛组相比亦有所上调。结论 microRNAs分子表达谱在AD不同证型患者皮损中存在差异表达,其介导的不同免疫炎症组织损伤可能是AD不同临床表现的物质基础。

OBJECTIVE To explore the relationship between expression profiles of microRNAs and chemokines and Chinese medicine syndromes in the skin lesions of patients with atopic dermatitis. METHODS 79 patients of AD were divided into three groups（group of internal damp-heat accumulation, group of excessive dampness due to spleen deficiency and group of blood deficiency and wind-dryness） according to syndrome differentiation. The qPCR and immunohistochemistry techniques were used to detect the expression characteristics of five microRNAs and three cbemokines related to skin inflammations in AD. Immunoregulation of these differential expressions were statistically analyzed. RESULTS Increased expression levels of miR21 and decreased expression levels of miR125b were seen in the group of internal damp-heat accumulation, which were sig- nificantly different from the normal control group and the group of blood deficiency and wind-dryness（P^0.01）. At the same time the higher expression of TARC/CCL17 was rloticed and the positive molecules were seen located in the basal layer of the epidermis and dermis. The expression of miR-155 was significantly higher than the other two groups and the normal control group in the group（P % 0.01）. The expression of miR203 decreased, but no statistically significant difference were noticed when compared to the other groups（P~〉0.05）. The highest expression of CTACK/CCL27 molecules were seen scattered in the epidermis and dermis. In the group of blood deficiency and wind-dryness, miR-146 expression has been raised, with significant statistical difference from the other groups（P〈0.01）. RANTES/CCL5 expression increased, higher than the group of internal damp-heat accumulation（P〈0.01）. The same change was seen for TARC/CCL17 expression. CONCLUSION The microR- NA expression profiles differentially expressed in AD patients with different syndromes, leading to different inflammatory tis-sue damages. These findings reveal the pathogenesis molecular mechanisms of AD.