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

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。

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

Objective: To observe the changes of pulmonary function and Notch signaling pathway oflung tissues in adjuvant-induced arthritis rats, and to investigate the mechanism of reduced lungfunction.Methods: A total of 30 rats were randomly divided into a normal group and a model group. Ratsin the model group were induced to establish the adjuvant arthritis AA model by intradermallyinjecting 0.1 mL Freund's complete adjuvant into the right paw. After 30 days, we observed the pawedema volume, arthritis index, pulmonary function, histomorphology, and Notch receptor/ligandof the lung tissue.Results: Compared with the normal group, the paw edema volume, arthritis index, averageexpiratory flow within 0.3 s (FEV0.3/FVC), and the level of Notch3, Notch4 and Jagged2 of the lungtissue in the model group was significantly increased, while maximum expiratory flow at 50% ofvital capacity (FEF50), maximum expiratory flow at 75% of vital capacity (FEF75), forced expiratoryflow (PEF) and the expression of Notch1 of Jagged1 and Delta1 in the lung were significantlydecreased (P<0.05, P<0.01). There were significant positive correlations between FEV0.3/FVC andNotch4. FEV0.3/FVC, FEF25, FEF50 and Notch3, Delta1 were negatively correlated, respectively(P<0.05, P<0.01).Conclusion: While arthritis occurs in AA rats, pulmonary function declines and significantlycorrelates with the expression of Notch receptor/ligand. The deposition of immune complex in thelung after the injection of CFA activates the Notch signaling pathway, and results in further declineof pulmonary function by signaling cascades.