益气养阴祛瘀方调节B细胞IRF7基因启动子区DNA甲基化/羟甲基化平衡改善SS唾液腺损伤的机制研究

免疫相关基因启动子区的DNA甲基化/羟甲基化的表观遗传学修饰可以通过诱导免疫细胞异常活化、增殖炎症因子及自身抗体分泌来促进干燥综合征（Sjögren’s syndrome,SS）的发生、进展。B细胞中I型干扰素通路相关因子IRF7的DNA甲基化/羟甲基化修饰平衡破坏是SS发病的关键环节。我们前期研究发现，益气养阴祛瘀方能够调节I型干扰素信号通路表达而抑制SS的B细胞活化，改善唾液腺分泌功能。由此，我们提出了益气养阴祛瘀方能调节B细胞IRF7基因启动子区DNA甲基化/羟甲基化平衡，减轻唾液腺损伤的科学假说。本课题拟利用质粒转染、焦磷酸测序等现代生物学技术，从人体、动物实验和细胞实验方面，研究益气养阴祛瘀方对B细胞IRF7基因启动子区DNA甲基化/羟甲基化水平及其对SS唾液腺损伤的影响。从表观遗传学角度，探索益气养阴祛瘀方治疗SS的机制，为中医药治疗SS提供新的靶点和理论依据。

Epigenetic modification of DNA methylation and hydroxymethylation in the promoter region of immune-related genes can promote the occurrence and progression of Sjögren's syndrome (SS) by inducing abnormal activation of immune cells, proliferation of inflammatory factors, and autoantibody secretion.The disruption of DNA methylation and hydroxymethylation modification balance of type I interferon pathway-related factor IRF7 in B cells is the key link in the pathogenesis of SS.Our previous research found that Yiqi Yangyin Quyu Recipe can regulate the expression of the type I interferon signal pathway, inhibit the B cell activation of SS, and improve the salivary gland secretion function.Therefore, we proposed the scientific hypothesis that Yiqi Yangyin Quyu Recipe can regulate the balance of DNA methylation and hydroxymethylation in the promoter region of IRF7 gene of B cells and reduce salivary gland damage.This project intends to use modern biological technologies such as plasmid transfection and pyrosequencing to study the DNA methylation and hydroxymethylation level on B cell IRF7 gene promoter region and its effect on salivary gland injury in SS of Yiqi Yangyin Quyu Recipe from human, animal and cell experiments.From the perspective of epigenetics, explore the mechanism of Yiqi Yangyin Quyu Recipe for treating SS, and provide new targets and theoretical basis for Chinese medicine treatment of SS.