Notch-Jagged/Delta信号通路在佐剂关节炎大鼠肺功能降低中的作用  

Role of Notch-Jagged/Delta signaling pathway in arthritis rats of reduced lung function induced by adjuvant

作　　者：万磊[1] 刘健[1] 黄传兵[1] 汪元[1] 张晓军[2] 阮丽萍[3] 王亚黎[3] 叶文芳[3] 

机构地区：[1]安徽中医药大学第一附属医院,合肥230031 [2]湖北中医药大学研究生院,武汉430065 [3]安徽中医药大学研究生院,合肥230038

出　　处：《中南大学学报（医学版）》2014年第2期109-116,共8页Journal of Central South University ：Medical Science

基　　金：国家自然科学基金(81173211);国家中医药重点学科中医痹病学建设项目(国中医药发[2009]30号);安徽省科技厅科研计划项目(09020304046);安徽省卫生厅中医药科研项目(2009ZY05);安徽现代中医内科应用基础与开发研究省级实验室建设项目(科条[2008]150号);安徽中医学院科技创新团队项目(2010TD005)~~

摘　　要：目的:观察佐剂关节炎(AA)大鼠肺功能、肺组织Notch信号通路的变化,探讨AA大鼠肺功能降低的机制。方法:将30只大鼠随机分为正常组和模型组,每组15只,向模型组大鼠右后足跖皮内注射弗氏完全佐剂0.1 mL致炎,复制成AA模型。致炎30 d后,观察两组大鼠足跖肿胀度、关节炎指数、肺功能、肺病理形态学及肺组织Notch受体/配体表达的变化。结果:与正常组相比,模型组大鼠足跖肿胀度、关节炎指数、肺功能参数0.3 s内平均呼气流量(FEV0.3/FVC)、肺泡炎程度、肺组织Notch3和Notch4及Jagged2的表达升高(P<0.05或P<0.01);50%肺活量的最大呼气流量(FEF50)、75%肺活量的最大呼气流量(FEF75)、用力最大呼气流量(PEF)降低,肺组织Notch1,Jagged1,Delta1的表达降低(P<0.01)。相关分析显示:大鼠肺功能参数FEV0.3/FVC与Notch4呈正相关,FEV0.3/FVC,FEF25,FEF50分别与足跖肿胀度,Notch3,Delta1的表达呈负相关(P<0.05或P<0.01)。结论:AA大鼠在发生足跖肿胀、关节炎症同时出现肺功能降低,且肺功能参数与Notch受体/配体呈相关性,提示致炎后免疫复合物沉积于组织局部,激活Notch信号通路,通过级联放大效应协同参与肺组织损伤,导致肺功能降低。Objective: To observe the changes of pulmonary function and Notch signaling pathway of lung tissues in adjuvant-induced arthritis rats, and to investigate the mechanism of reduced lung function. Methods: A total of 30 rats were randomly divided into a normal group and a model group. Rats in the model group were induced to establish the adjuvant arthritis AA model by intradermally injecting 0.1 mL Freund's complete adjuvant into the right paw. At er 30 days, we observed the paw edema volume, arthritis index, pulmonary function, histomorphology, and Notch receptor/ligand of the lung tissue. Results: Compared with the normal group, the paw edema volume, arthritis index, average expiratory l ow within 0.3 s(FEV 0.3 /FVC), and the level of Notch3, Notch4 and Jagged2 of the lung tissue in the model group was significantly increased, while maximum expiratory flow at 50% of vital capacity(FEF 50), maximum expiratory l ow at 75% of vital capacity(FEF 75), forced expiratory flow(PEF) and the expression of Notch1 of Jagged1 and Delta1 in the lung were significantly decreased(P<0.05, P<0.01). h ere were signii cant positive correlations between FEV 0.3 /FVC and Notch4. FEV 0.3 /FVC, FEF 25, FEF 50 and Notch3, Delta1 were negatively correlated, respectively(P<0.05, P<0.01). Conclusion: While arthritis occurs in AA rats, pulmonary function declines and significantly correlates with the expression of Notch receptor/ligand. h e deposition of immune complex in the lung at er the injection of CFA activates the Notch signaling pathway, and results in further decline of pulmonary function by signaling cascades.

关 键 词：佐剂关节炎 肺功能 Notch1~4 Jagged1~2 Delta1 

分 类 号：R285.5[医药卫生—中药学]