目的观察新风胶囊(XFC)对肺泡Ⅱ型上皮细胞Notch/Jagged/HES影响。方法大鼠分为正常对照组、模型组、来氟米特(LEF)组、XFC组,除正常对照组外,其余3组复制佐剂关节炎大鼠模型。致炎后第13天给药,每天1次,连续给药30 d。正常对照组、模型组给予生理盐水灌胃,每天1次;LEF组给予LEF(0.5 mg/100 g)灌胃、XFC组给予XFC(0.034 g/100 g)灌胃,观察大鼠足跖肿胀度、关节炎指数、肺功能,透射电镜观察大鼠肺泡Ⅱ型上皮细胞超微结构,Western blot法检测肺泡Ⅱ型上皮细胞转化生长因子β1(TGF-β1)、Notch1、Notch3、Jagged1、HES1蛋白表达。结果模型组大鼠肺功能参数最大呼气第一秒呼出的气量的容积(FEV1)、50%肺活量的呼气流量(FEF50)、75%肺活量的呼气流量(FEF75)、用力最大呼气流量(PEF)较NC组显著降低,肺泡Ⅱ型上皮细胞超微结构破坏,肺泡Ⅱ型上皮细胞TGF-β1、Notch1、Notch3、Jagged1、HES1表达升高。与模型组比较,XFC组FEV1、FEF50、FEF75、PEF均显著升高,TGF-β1、Notch1、Notch3、Jagged1、HES1降低。XFC组较LEF组肺功能升高。结论 XFC通过下调TGF-β1、Notch1、Notch3、Jagged1、HES1,抑制肺间质纤维化,改善肺功能。
Objective To observe the effect of Xinfeng Capsule( XFC) on Notch/Jagged-HES of type Ⅱ alveolar epithelial cells( AECⅡ). Methods Rats were divided for four groups: normal control( NC) group,model control( MC) group,leflunomide( LEF) group,XFC group,with 10 rats in each group. Complete Freund's adjuvant( CFA) was injected in the right foot plantar skin of each rat except for the NC group. After adjuvant arthritis was successfully induced,LEF group was given LEF( 0. 5 mg/100 g),and XFC group was treated with XFC( 0. 034 g/100 g),once a day from the 13 th day to the 42 th day. The NC and MC groups were given normal saline instead. Swelling degree( SD),arthritis index( AI) and pulmonary function were observed. AECⅡ was observed by transmission electron microscopy( TEM). The expressions of transforming growth factor β1( TGF-β1),Notch1,Notch3,Jagged1 and HES1 proteins in AEC Ⅱ were detected by Western blotting.Results The pulmonary function parameters such as forced expiratory volume in 1 second( FEV1),maximum expiratory flow rate at 50% FVC( FEF50),instantaneous flow at 75% of expired volume( FEF75),peak expiratory flow( PEF) in the MC group were significantly lower than those in the NC group,and the expressions of TGF-β1,Notch1,Notch3,Jagged1 and HES1 in AECⅡ increased. The ultrastructure of AECⅡ was damaged. Compared with the MC group,FEV1,FEF50,FEF75 and PEF increased,and TGF-β1,Notch1,Notch3,Jagged1 and HES1 decreased in the XFC group. Compared with LEF group,the lung function was better in XFC group. Conclusion XFC can inhibit pulmonary fibrosis and improve pulmonary function by down-regulating TGF-β1,Notch1,Notch3,Jagged1 and HES1 in rats with adjuvant arthritis.