基于上皮-间质转化及血管新生探讨麦门冬汤对特发性肺纤维化大鼠的作用机制OA

Objective It is to investigate the effect and its possible mechanism of Maimendong Decoction(MD)in the treatment of idiopathic pulmonary fibrosis(IPF).Methods Sixty Wistar rats were divided into 6 groups,with 10 rats in each group.The rats of all groups except for the normal group were given bleomycin(BLM)via intratracheal injection to establish models of IPF.After successful modeling,the low-dose,medium-dose and high dose groups of MD were given MD 7.5 g/kg,15 g/kg,30 g/kg via gavage,the prednisone acetate group was given prednisone acetate 6.25 mg/kg via gavage,the normal group and model group were given the same amount of normal saline via gavage,all once daily,contin-uously treated for 3 weeks.The lung function parameters[forced vital capacity(FVC),peak expiratory flow(PEF),total lung resistance(RL)and dynamic compliance(Cydn)]of rats in each group were detected,the lung tissue pathology was observed using HE staining and Masson's staining,the positive expressions of E-cadherin(E-cad),α-smooth muscle actin(α-SMA)and Collagen Ⅰ,as well as microvascular density(CD34 labeling)were detected by immunohistochemistry,the mRNA expressions of E-cad,α-SMA,Collagen Ⅰ,vascular endothelial growth factor(VEGF)and fibroblast growth factor 2(FGF2)in lung tissue were detected by Real-time quantitative PCR.Results Compared with the control group,the FVC,PEF and Cydn of rats in the model group were significantly reduced(all P<0.05),while the RL,alveolitis scores,and pulmonary fibrosis scores of the rats were significantly increased(all P<0.05);the mean optical density of E-cad positive expression and the relative expression of E-cad mRNA in lung tissue of the rats were both significantly reduced(all P<0.05),while the mean optical densities of α-SMA and Collagen Ⅰ positive expressions,microvascular density,and the relative mRNA expressions of α-SMA,Collagen Ⅰ,VEGF,and FGF2 in lung tissue of the rats were all significantly increased(all P<0.05).Compared with the model group,the FVC,PEF and Cydn of rats in the medium-dose and high dose groups of MD and prednisone acetate group were significantly increased(all P<0.05),while the RL,alveolitis scores,and pulmonary fibrosis scores of the rats were significantly decreased(all P<0.05);the mean optical density of E-cad positive expression and the relative expression of E-cad mRNA in lung tissue of the rats were both significantly in-creased(all P<0.05),while the mean optical densities of α-SMA and Collagen Ⅰ positive expressions,microvascular density,and the relative mRNA expressions of α-SMA,Collagen Ⅰ,VEGF,and FGF2 in lung tissue of the rats were all significantly decreased(all P<0.05).Conclusion MD can significantly alleviate the degree of pulmonary interstitial fibro-sis and lung tissue damage and improve lung function of rats with IPF,and its mechanism may be related to inhibiting epi-thelial-mesenchymal transition and angiogenesis.