雷公藤甲素对佐剂关节炎肺功能降低大鼠Notch通路受体和配体基因表达的影响  

Effect of triptolide on expressions of Notch receptors and ligands in rats with adjuvantinduced arthritis and reduced pulmonary function

作　　者：万磊[1] 刘健[1] 黄传兵[1] 谌曦[1] 汪元[1] 张皖东[1] 刘磊[1,2] 程园园[3] 冯云霞[4] 

机构地区：[1]安徽中医学院第一附属医院风湿免疫科,安徽合肥230031 [2]安徽中医药大学中医临床学院,安徽合肥230038 [3]安徽省安庆市中医院内科,安徽安庆246000 [4]安徽中医药大学中西医结合医院,安徽合肥23000

出　　处：《南方医科大学学报》2015年第10期1390-1394,共5页Journal of Southern Medical University

基　　金：国家自然科学基金(81173211);国家自然基金青年项目(81403388);安徽省自然基金项目(1508085QH159);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);安徽中医学院科技创新团队项目(2010TD005);安徽中医药大学校级基金(2014qn025)~~

摘　　要：目的观察雷公藤甲素(TPT)对佐剂关节炎(AA)大鼠Notch受体、配体表达的影响。方法将40只大鼠随机分为正常对照(NC)组、模型(MC)组、甲氨喋呤(MTX)组、TPT组,每组10只,分别向除NC组外的其余动物右后足跖皮内注射弗氏完全佐剂0.1 m L致炎,复制AA大鼠模型,致炎后第12填开始给药。NC组及MC组均给予生理盐水,其余组分别给予MTX、TPT。给药30 d后,检测各组足趾肿胀度(E)、关节炎指数(AI)、肺功能、Notch受体/配体的变化。结果 MC组大鼠E、AI、Notch3、Notch4、Delta1表达明显升高;肺功能参数、Notch1、Jagged1、Jagged2表达降低(P<0.01);与MC组比较,TPT组肺功能参数、Notch1、Jagged1、Jagged2的表达升高,E、AI及Notch3、Notch4、Delta1表达降低,疗效优于对照组MTX(P<0.05,P<0.01)。结论 TPT可能是通过上调Delta1、Notch3、Notch4的表达、下调Jagged1、Jagged2、Notch1表达,降低炎症反应和免疫复合物沉积,改善AA关节和肺部症状。Objective To investigate the effects of triptolide on Notch receptor and ligand expressions in rats with adjuvantinduced arthritis（AA）. Methods Forty rats were randomly divided into normal control（NC） group, model（MC） group,methotrexate group and triptolide groups. Rat models of AA were established by an intradermal injection of 0.1 mL Freund＇s complete adjuvant into the right paw. Twelve days after the injection, the rats were treated with corresponding drugs for 30days; the rats in NC group and MC group were given saline only. Paw edema volume（E）, arthritis index（AI）, pulmonary function, histomorphologies, and Notch receptor/ligand expression in the lung tissue were analyzed after the treatments.Results Compared with the NC group, E, AI, Notch3, Notch4, and Delta1 expressions in the lung tissues significantly increased while pulmonary function and pulmonary expressions of Notch1, Jagged1, and Jagged2 significantly decreased the model rats（P〈0.01）. Compared with the MC group, triptolide-treated rats showed significantly improved pulmonary functions, increased expressions of Notch1, Jagged1, and Jagged2 and decreased expressions of Notch3, Notch4, and Delta1 in the lungs（P〈0.05, P〈0.01）; the therapeutic effect of triptolide was better than that of methotrexate. Conclusion Triptolide can reduce inflammatory reaction and immune complex deposition to improve joint and pulmonary symptoms in rats with AA possibly by up-regulating the expressions of Notch3, Notch4, and Delta1 and down-regulating the expressions of Jagged1,Jagged2, and Notch1.

关 键 词：佐剂关节炎 肺功能 NOTCH信号通路 雷公藤多甲素 

分 类 号：R285.5[医药卫生—中药学]