佐剂关节炎大鼠肺功能变化与Notch1、Notch2/Jagged1、Jagged2通路的相关性  

Correlation between changes of pulmonary function and Notch1, Notch2/Jagged1,Jagged2 signaling pathway in adjuvant arthritis rats

作　　者：万磊[1] 刘健[2] 程园园[3] 冯云霞[3] 刘磊[3] 黄传兵[2] 汪元[2] 

机构地区：[1]湖北中医药大学研究生院,武汉430065 [2]安徽中医学院第一附属医院风湿免疫科,合肥230031 [3]安徽中医学院研究生院,合肥230038

出　　处：《安徽医科大学学报》2012年第10期1156-1160,共5页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:81173211);国家中医药重点学科中医痹病学建设项目(编号:国中医药发[2009]30号);安徽省科技厅科研计划项目(编号:09020304046);安徽省卫生厅中医药科研项目(编号: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(编号:科条〔2008〕150号);安徽中医学院科技创新团队项目(编号:2010TD005)

摘　　要：目的观察佐剂关节炎(AA)大鼠肺功能降低与肺组织Notch1、Notch2、Jagged1、Jagged2的关系。方法将40只大鼠随机均分为正常组和模型组,模型组大鼠右后足跖皮内注射弗氏完全佐剂(CFA)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、肺组织形态学变化,RT-PCR法检测肺组织Notch1、Notch2及Jagged1、Jagged2的表达。结果模型组大鼠足跖肿胀度、关节炎指数升高,肺功能参数用力肺活量(FVC)、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、Jag-ged1、Jagged2的表达水平降低(P<0.05,P<0.01)。相关分析显示,模型组大鼠肺功能参数FVC与Jagged1呈正相关,1s内平均呼气流量(FEV1/FVC)与Notch1呈正相关,FEF50与Jagged2呈正相关,FEF75与Notch1、Notch2呈正相关,与Jag-ged1呈负相关(P<0.05,P<0.01)。结论 AA大鼠在发生关节炎症的同时出现肺功能降低,而肺功能降低与Notch受体/配体呈高度相关,提示致炎后形成的免疫复合物沉积于肺组织,激活肺组织Notch信号通路,通过级联放大效应进一步导致肺功能降低。Objective To evaluate the correlation between decline of pulmonary function and Notch1, Notch2/Jaggedl, Jagged2 signaling pathway in adjuvant arthritis rats （AA rats）. Methods 40 AA rats were randomly divided into normal group and model group. Rats in MC group were induced to AA model by intradermally injecting 0. 1 ml Freund＇s complete adjuvant into the right paw. After 30 days, paw edema volume, arthritis index, pulmonary function, histo-morphological changes of pulmonary were observed, and the expressions of Notchl, Notch2/Jaggedl, Jagged2 by RT-PCR of AA rats were detected. Results Compared with NC group, paw edema volume, arthritis index in MC group significantly increased, while FVC, FEFs0, FEF75, PEF and the expressions of Notchl, Jagged1, Jagged2 in lungs significantly decreased （P 〈0. 05 ,P 〈0. 01 ）. The correlation analysis indicated that there were significant positive correlations between FVC and Jaggedl, FEVI/FVC and Notchl, FEFso and Jagged2; FEF75 was positively correlated with MAC and MDC respectively, while negatively correlated with Jaggedl （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, suggesting that the deposition of immune complex in pulmonary following injection of CFA activates Notch signaling pathway, and results in further decline of pulmonary function by signalirig cascades.

关 键 词：佐剂关节炎 肺功能 Notch1~2 Jagged1~2 

分 类 号：R593.2[医药卫生—内科学]