黄芪提取物对特发性肺纤维化小鼠的治疗效果及TGF-β、VEGF分析

Therapeutic Effect of Astragalus Membranaceus Extract on Mice with Idiopathic Pulmonary Fibrosis and Influence on TGF-βand VEGF

目的探讨黄芪提取物对特发性肺纤维化小鼠的治疗效果及对小鼠转化生长因子-β(transforming growth factor-β,TGF-β)、血管内皮生长因子(vascular endothelial growth factor,VEGF)的影响。方法选择200只健康雄性SPF级KM小鼠作为研究对象,采取随机数字表法分为假手术组、模型组、黄芪总黄酮组、黄芪多糖组、黄芪总皂苷组,每组40只小鼠。除假手术组外,各组小鼠均进行气管内滴注博莱霉素,假手术组予以等量生理盐水滴入气管内,造模后,黄芪总黄酮组、黄芪多糖组、黄芪总皂苷组小鼠分别给予相应药物,假手术组、模型组均给予生理盐水,持续28 d。比较5组小鼠的单核细胞浓度、巨噬细胞浓度、肺泡炎评分、肺纤维化评分、TGF-β、VEGF。结果(1)黄芪总黄酮组、黄芪多糖组、黄芪总皂苷组的单核细胞浓度、巨噬细胞浓度均较模型组更低(P<0.05);黄芪总黄酮组的单核细胞浓度、巨噬细胞浓度均较黄芪多糖组、黄芪总皂苷组更低(P<0.05)。(2)黄芪总黄酮组、黄芪多糖组、黄芪总皂苷组的肺泡炎评分、肺纤维化评分均较模型组更低(P<0.05),黄芪总黄酮组的肺泡炎评分、肺纤维化评分均较黄芪多糖组、黄芪总皂苷组更低(P<0.05)。(3)经免疫组化检测、蛋白质印迹杂交法检测,黄芪总黄酮组、黄芪多糖组、黄芪总皂苷组的TGF-β、VEGF水平均较模型组更低(P<0.05);黄芪总黄酮组的TGF-β、VEGF水平均较黄芪多糖组、黄芪总皂苷组更低(P<0.05)。结论黄芪总黄酮、黄芪多糖、黄芪总皂苷均可有效减轻特发性肺纤维化小鼠的炎症反应、肺纤维化,抑制TGF-β、VEGF表达,尤其是黄芪总黄酮,其抗纤维化作用在各种黄芪提取物中最显著。

Objective To investigate the therapeutic effect of Astragalus membranaceus L.extract on mice with idiopathic pulmonary fibrosis and the influence on the expressions of transforming growth factor-β(TGF-β)and vascular endothelial growth factor(VEGF)in mice.Methods A total of 200 healthy male SPF KM mice were selected as subjects.They were randomly divided into sham operation group,model group,total flavonoids of Astragalus membranaceus,Astragalus polysaccharide group and Astragalus saponin group,40 mice in each group.Except for the sham operation group,each group’s mice underwent intratracheal instillation of bleomycin,and the sham operation group was given the same amount of normal saline into the trachea.After modeling,the total flavonoids of Astragalus membranaceus,Astragalus polysaccharide group,and total saponins of Astragalus membranaceus groups’mice were given the corresponding drugs,and the sham operation group and the model group were given normal saline for 28 days.Monocyte concentration,macrophage concentration,alveolitis score,pulmonary fibrosis score,TGF-βand VEGF were compared among the 5 groups.Results(1)The concentrations of mononuclear cell concentration and macrophage of total flavonoids,astragalus polysaccharides and total saponins of Astragalus membranaceus were lower than those of the model group(P<0.05).The concentrations of mononuclear cell and macrophages of total flavonoids of Astragalus membranaceus were lower than those of Astragalus polysaccharide group and Astragalus total saponin group(P<0.05).(2)The alveolitis score and pulmonary fibrosis score of the total flavonoids group,Astragalus polysaccharide group and Astragalus membranaceus group were lower than those of the model group(P<0.05).The alveolitis score and pulmonary fibrosis score of the total flavonoids of Astragalus membranaceus group were lower than that of Astragalus polysaccharide group and Astragalus total saponin group(P<0.05).(3)The levels of TGF-βand VEGF in the total flavonoids group,astragalus polysaccharide group and total saponin group were lower than those in the model group by immunohistochemistry and Western blot hybridization(P<0.05).The levels of TGF-βand VEGF in the total flavonoids of Astragalus group were lower than those in the astragalus polysaccharide group and the total saponin group(P<0.05).Conclusion Astragalus flavonoids,Astragalus polysaccharides and Astragalus saponins can effectively alleviate the inflammatory reaction,pulmonary fibrosis and inhibit the expressions of TGF-βand VEGF in mice with idiopathic pulmonary fibrosis,especially the total flavonoids of Astragalus membranaceus.The effect is most pronounced in various extracts of Astragalus.