Notch1-Dll4信号通路在桥本甲状腺炎自身免疫损伤中的作用  

Role of Notch-Dll4 signaling pathway in autoimmune damage of Hashimoto thyroiditis

作　　者：张悦[1] 宋守君[1] 薛海波[1] 马蕾[2] 袁厉兵 杜向荣 Zhang Yue,Song Shoujun,Xue Haibo,Ma Lei,Yuan Libing,Du Xiangrong(Department of Endocriology,Affiliated Hospital of Binzhou Medical University, Binzhou 256603, China)

机构地区：[1]滨州医学院附属医院内分泌科,256603 [2]滨州医学院附属医院皮肤科,256603

出　　处：《中华内分泌代谢杂志》2018年第10期852-855,共4页Chinese Journal of Endocrinology and Metabolism

基　　金：山东省重点研发计划（2016GSF201021）,山东省高等学校科技计划（J16LL01）

摘　　要：选择40例桥本甲状腺炎（HT）患者（HT组）和20名健康对照者（NC组），将HT患者进一步分为甲状腺功能正常组（HT-A）和临床甲状腺功能减退组（HT-B）。实时定量PCR检测外周血单个核细胞（PBMCs）中Notch1、Dll4、维甲酸受体相关孤儿受体（ROR）-γt mRNA的表达水平，流式细胞术检测PBMCs中Th17细胞的比例，电化学发光免疫分析检测甲状腺功能、甲状腺过氧化物酶抗体（TPOAb）、甲状腺球蛋白抗体（TgAb）水平。结果显示，HT组Notch1、Dll4、ROR-γt mRNA水平及Th17细胞比例均高于NC组（均P〈0．01），尤其在HT-B组升高更为明显。另外，在HT组中Notchl、D114 mRNA表达水平与Th17细胞比例及其转录因子ROR-γt mRNA的表达水平（均P〈0．01）呈显著正相关，与血清TPOAb、TgAb滴度亦呈显著正相关（P〈0．05或P〈0．01）。这些结果提示Notch1-Dll4信号通路可能通过调控Th17细胞参与HT患者甲状腺自身免疫损伤的发生机制。Forty patients with Hashimoto thyroiditis （HT） and 20 healthy subjects with matched age-and sex-features （ NC ） were selected. The patients with HT were further divided into normal thyroid function （HT-A） and hypothyroidism （HT-B） groups. Real-time PCR was performed to evaluate the expressions of Notchl, Dl14, and retinoid-related orphan receptor （ ROR）-γt mRNA. Flow-cytometry was used to detect the percentage of Th17 cells. Thyroid function, thyroid peroxidase antibody （TPOAb）, and thyroglobulin antibody （TgAb） were detected by electrochemiluminescence immunoassaies. The results showed that the Notchl, Dl14, ROR-γt mRNA levels and Th17 cell percentage were significantly increased in HT group compared with NC group （ all P〈0.01 ）, especially in HT-B group. In HT patients, Notchl and Dll4 mRNA expression levels were positively correlated with Thl7 ceil percentage and its transcription factor ROR-γt （ all P〈0.01 ）. Besides, there were significantly positive correlations of Notch 1 and Dl14 mRNA expressions with TPOAb and TgAb titers （P〈0.05 or P〈0.01 ）. These results suggest that Notchl-Dll4 signaling pathway might be involved in the pathogenesis of thyroid-specific autoimmune damage by regulating Th17 cells in HT patients.

关 键 词：桥本甲状腺炎 Notch1-Dll4信号通路 TH17细胞 自身免疫 

分 类 号：R581.4[医药卫生—内分泌]