let-7a通过调控BAFF参与嗜酸粒细胞性CRSwNP发病机制的研究

The exact pathogenesis of eosinophilic chronic rhinosinusitis with nasal polyp(CRSwNP) remains unclear. BAFF has been implicated in Eos CRSwNP. Our recent study showed that miR-125b contributes to pathogenesis of Eos CRSwNP by regulating BAFF indirectly.let-7a was found to be downregulated in Eos CRSwNP and correlated negatively with BAFF protein expression. Bioinformatic analysis indicated potential binding of let-7a to the BAFF 3'untranslated region.These findings lead to the hopothesis that let-7a contribute to pathogenesis of Eos CRSwNP through targeting BAFF.This study is designed to 1.demonstrate the regulation of BAFF by let-7a by means of luciferase reporter assays;2.explore the effect of let-7a on immunopathologic characteristics and BAFF expression in experimental eosinphilic CRS by overexpression of let-7a.Our study is aimed to demonstrate the mechanism by which let-7a contributes to inflammatory process of Eos CRSwNP through targeting BAFF.

嗜酸粒细胞性伴鼻息肉的慢性鼻-鼻窦炎（Eos CRSwNP）的发病机制尚不清楚。有研究表示B细胞激活因子（BAFF）在Eos CRSwNP中起重要作用。miRNA是近年来发现的重要调控因子。我们前期研究显示miR-125b通过间接调控BAFF在Eos CRSwNP发病中起重要作用。我们发现let-7在Eos CRSwNP表达下降,与BAFF表达呈负相关，信息生物学方法显示BAFF 3'非翻译区与let-7a互补结合。综合以上结果，我们推测let-7通过调控靶基因BAFF参与Eos CRSwNP发病。我们拟1.采用报告基因技术，研究let-7a负向调控BAFF；2.建立小鼠嗜酸粒细胞性鼻-鼻窦炎模型，过表达let-7a，动态观察小鼠体内let-7a对BAFF表达及Eos CRSwNP病理免疫学特征的影响。本研究有助于阐明let-7a通过调控BAFF参与Eos CRSwNP炎症反应的机制。

慢性鼻窦炎（CRS）的发病机制尚不清楚。 B细胞刺激因子(BAFF)和肿瘤坏死因子受体2（TNFRSF1B）在慢性鼻窦炎发病和生物膜的形成中起重要作用。miRNA是新近发现的重要调控因子。我们阐明了let-7a参与了CRS发病。首先我们采用信息生物学方法预测可能BAFF和TNFRSF1B是let-7a的靶基因。然后采用荧光素酶报告基因技术和细胞转染技术，验证了离体环境下let-7能负向调控TNFRSF1B和BAFF；继而建立小鼠嗜酸粒细胞性鼻窦炎过表达let-7模型，动态观察小鼠体内let-7a对BAFF和TNFRSF1B的表达、CRS生物膜的影响。本研究描绘了let-7a通过调控BAFF和TNFRSF1B表达，参与CRSwNP炎症过程中的作用机制。