口腔颌面外科杂志2016，Vol.26Issue(4)：256-263,8.DOI:10.3969/j.issn.1005-4979.2016.04.005
TLR9依赖的p38MAPK信号通路对鼠原发性舍格伦综合征的影响
Inhibition of TLR9-dependent p38MAPK Signaling Pathway Attenuates the Pathogenesis of primary Sjögren's Syndrome in Mouse
摘要
Abstract
Objective: To observe whether the inhibition of TLR9-dependent p38 MAPK pathway are associated with at-tenuation of symptoms and signs in the pathogenesis of primary Sjögren's syndrome (pSS). Methods: NOD/Ltj mice were selected as a model of pSS and Balb/c mice were used as control group. NOD/Ltj mice were treated by 3 inhibitors:ODN2088, VX-702, and hydroxychloroquine respectively. The changes of stimulated salivary flow rate was measured and the histopathology of submandibular gland was evaluated by HE stain. Peripheral blood mononuclear cells (PBMCs) de-rived from NOD and Balb/c mice were analysis by flow cytometry. The plasma derived from peripheral blood of NOD and Balb/c mice was analyzed by ELISA. Tunel method to detect epithelial cell apoptosis was performed on submandibular gland sections in NOD mice and Balb/c mice. Results: Compared with NOD/Ltj mice, only the salivary secretion of NOD/Ltj mice given ODN2088 was significantly increased. Periductal inflammatory cell foci were observed in the submandibularglands in the whole NOD mice given hydroxychloroquine, 1/5 of the NOD mice given ODN2088 and all of the NOD mice without any treatment. There were no lymphocytes foci in the NOD mice received VX-702. The number of lymphocytes was extremely low in NOD mice given VX-702, the NOD mice given ODN2088 and NOD mice given hydroxychloroquine. Titers of anti-SSA/Ro and anti-SSB/La in plasma of NOD mice given ODN2088 were the lowest among all groups. Conclusion:Inhibition of TLR9-dependent p38MAPK signaling pathway could alleviate the clinical symptoms of pSS to a certain extent. In addition, The activation of TLR9-dependent p38MAPK signaling pathway palys an important role in the patho-genesis of pSS in NOD/Ltj mice.关键词
原发性舍格伦综合征/非肥胖型糖尿病鼠 (NOD鼠)/Toll样受体 (TLR9)/p38 MAPK/流式细胞术/抑制剂Key words
primary Sjögren's syndrome/NOD/TLR9/p38 MAPK/flow cytometry/inhibitor分类
医药卫生引用本文复制引用
曹宁宁,郑凌艳,俞创奇,石欢,高绮曼,陈婵..TLR9依赖的p38MAPK信号通路对鼠原发性舍格伦综合征的影响[J].口腔颌面外科杂志,2016,26(4):256-263,8.基金项目
国家自然科学基金资助项目(81100766)；上海市重点学科建设项目 （81100766）
