变应性鼻炎（AR）影响全球近40%的人口，尽管临床上我们有多种治疗方式，但患者对症状控制并不满意。申请人前期研究发现：AR患者鼻黏膜上皮细胞中组蛋白去乙酰化酶（HDAC）8表达增高，乙酰化Smad7表达降低、紧密连接（TJs）蛋白表达降低。HDAC8特异性抑制剂可以降低尘螨致敏AR小鼠鼻组织HDAC8高表达、升高乙酰化Smad7和TJs低表达，对AR有治疗作用。遂提出HDAC8/Smad7/TJs这一AR发病机制，并拟通过鼻黏膜上皮细胞气液培养、尘螨致敏AR小鼠模型；使用HDAC8特异性抑制剂、Smad7-vshRNA、野生型和乙酰化突变型Smad7慢病毒过表达载体；采用RT-PCR、WB、IF、IP、ELISA技术，跨膜电阻和右旋糖苷通透率检测，观察鼻变态反应中HDAC8升高，与Smad7结合并使之乙酰化水平下降，失去对TJs的调节能力这一AR发病机制，为长期有效治疗AR提供理论依据。

Allergic rhinitis (AR) affects nearly 40% of the world's population. Although we already have a variety of clinical treatments, patients are still dissatisfied with symptom control. Applicant’s previous studies showed that the expression of histone deacetylase (HDAC) 8 in nasal epithelial cells of AR patients increased, the expression of acetylated Smad7 and tight junctions (TJs) protein decreased, comparing to healthy people. HDAC8 specific inhibitors can reduce the high expression of HDAC8 in nasal tissues of AR mice sensitized by dust mite, it can also increase the low expression of acetylated Smad7 and TJs, hence had a therapeutic effect on AR. Therefore the applicant propose the possible mechanism of AR pathogenesis of HDAC8/Smad7/TJs. We will use two models: human primary nasal epithelial cells air-liquid interface culture and dust mite sensitized AR mouse models, and we will evaluate the effects of HDAC8 specific inhibitor，Lentivirus Smad7-WT, Lentivirus Smad7-MU and Smad7-vshRNA in these two models. Using techniques of RT-PCR, WB, IF, IP and ELISA, measurement of transmembrane resistance and FD4 permeability, we will inspect whether HDAC8 up-regulated in nasal allergy will lead to the decrease of Smad7 acetylation level, and whether the low level of acetylation Smad7 will lose its ability to regulate TJs. This research will provide a theoretical basis for long-term and effective treatment of AR.