从miR-423-5p介导NOX4/ROS/NF-κB通路调控甲状腺滤泡细胞焦亡探讨疏肝健脾化痰行气方治疗高碘诱发桥本甲状腺炎的机制

桥本甲状腺炎（HT）是碘充足地区甲状腺功能减退最常见的原因，高碘诱导甲状腺滤泡细胞焦亡是HT发病的重要环节，NOX4/ROS/NF-κB通路活化介导了甲状腺细胞焦亡。前期研究表明，疏肝健脾化痰行气方治疗HT疗效确切，在HT患者外周血中miR-423-5p表达显著下调，可通过靶向NOX4，负性调控ROS生成。据此我们推测该方干预HT可能与上调miR-423-5p，抑制NOX4/ROS/NF-κB通路活化，减少甲状腺细胞焦亡有关。本项目拟采用高碘喂养的NOD.H-2h4小鼠和碘化钠诱导的人甲状腺滤泡上皮细胞株为研究对象，结合基因沉默和过表达技术，从体内外两个方面探讨疏肝健脾化痰行气方对miR-423-5p、NOX4/ROS/NF-κB通路以及甲状腺细胞焦亡的影响，阐明该方治疗HT的作用机理，为中医药治疗HT提供新的理论和实验依据，对于预防临床甲状腺功能减退症的发生具有重要意义。

Hashimoto's thyroiditis (HT) is the most common cause of hypothyroidism in iodine rich areas.The pyroptosis of thyroid follicular cells induced by excessive iodine is an important part of the pathogenesis of HT,the activation of NOX4/ROS/NF-κB pathway mediates the pyroptosis of thyroid follicular cells.Our previous studies have shown that Shuganjianpihuatanxingqi decoction is effective in treating HT, and the expression of miR-423-5p in the peripheral blood of HT patients was significantly down-regulated.It can negatively regulates the production of reactive oxygen species (ROS) through targeting Nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4).Therefore, we speculated that the intervention of Shuganjianpihuatanxingqi decoction on HT may through up-regulating the expression of miR-423-5p, inhibiting NOX4/ROS/NF-κB pathway and reducing the pyroptosis of thyroid follicular cells.In this study,we intend to adopt NOD.H-2h4 mice fed with excessive iodine and human thyroid follicular epithelial cells cultured by sodium iodide as the research object.Using gene silencing and overexpression technology,to explore the effects of Shuganjianpihuatanxingqi decoction on the expression of miR-423-5p, NOX4/ROS/NF-κB pathway and the pyroptosis of thyroid follicular cells both in vivo and in vitro.To clarify the mechanism of this decoction in treating HT, and to provide a new theoretical and experimental basis for the treatment of HT with traditional Chinese medicine,It may play a significant role in preventing the occurrence of clinical hypothyroidism.