芪白平肺胶囊可降低慢性阻塞性肺疾病钙调磷酸酶和活化T细胞核因子c3(NFATc3)的水平

Qibaipingfei Capsule down-regulate the levels of calcineurin and nuclear factor of activated T-cells isoform c3( NFATc3) in chronic obstructive pulmonary disease

目的通过建立慢性阻塞性肺疾病(COPD)痰瘀阻肺证大鼠模型,观察益气化痰祛瘀方-芪白平肺胶囊(QPC)对钙调磷酸酶(Ca N)-活化T细胞核因子c3(NFATc3)信号分子表达的影响,探讨QPC对COPD肺血管重构的干预机制。方法雄性SD大鼠60只,随机分为正常组、模型组、高、中、低剂量QPC组和硝苯地平组。采用游泳、烟熏、低氧,建立COPD痰瘀阻肺证大鼠模型;观察QPC对肺功能参数和大鼠的肺血管形态学的影响;通过实时荧光定量PCR检测大鼠肺组织Ca N和NFATc3mRNA的表达、Western blot法检测Ca N和NFATc3的蛋白表达。结果模型组大鼠第0.3秒用力呼气容量(FEV0.3),用力肺活量(FVC)和FEV0.3/FVC等肺功能参数值显著下降,高、中、低剂量QPC组和硝苯地平组的肺功能参数值均有不同程度的上升。模型组大鼠肺血管的管壁增厚,代偿性肺气肿形成。高、中、低剂量QPC组和硝苯地平组也存在血管壁增厚、肺泡扩张,但程度较轻。与正常组相比,模型组肺组织Ca N和NFATc3的mRNA和蛋白表达水平显著增加;与模型组相比,高、中、低剂量QPC以及硝苯地平组的Ca N和NFATc3的mRNA和蛋白表达量显著减低。结论 QPC可降低COPD肺组织Ca N、NFATc3的水平。

Objective To investigate the effect of Qibaipingfei Capsule （QPC） on the expressions of calcineurin （CAN） and nuclear factor of activated T-cells isoform c3 （ NFATc3 ） of rat models with phlegm and blood stasis syndrome of chronic obstructive pulmonary disease （ COPD）, and to explore the possible mechanism underlying the intervention of QPC in pulmonary vascular remodeling of COPD. Methods Sixty male Sprague-Dawley （SD） rats were randomly divided into a normal group, a model group, a positive group of nifedipine, a high dose group, a middle dose group and a low dose group of QPC. The rat models with phlegm and blood stasis syndrome of COPD were established by compound methods of forced swimming, smoking and hypoxia. Then the pulmonary function and the pathological alterations of pulmonary vessels were observed. Furthermore, the mRNA and protein levels of CaN and NFATc3 in the lung tissues were determined by real-time quantitative PCR and Western blot analysis. Results Compared with the normal group, the forced expiratory volume at 0.3 second （FEV0.3）, the forced vital capacity （FVC） and FEV0.3/FVC in the model group were significantly reduced, but compared with the model group, the values mentioned above were restored to different extents in the groups of nifedipine and QPC, The lung tissues of the model group showed the thickening of pulmonary vascular wall and the formation of compensating emphysema. The above pathological changes were relieved in all the treatment groups. Compared with the normal group, the expressions of CaN and NFATc3 in the model group were significantly up-regulated in transcription and translation levels. Compared with the model group, these expressions were down-regulated to various degrees in all the treatment groups. Condusion QPC can decrease the levels of CaN and NFATc3 in the lung tissues of COPD.