黄芪提取物对肺纤维化小鼠肺泡炎症影响及抗纤维化作用研究  

Impacts of Astragalus Extract on the Alveolar Inflammation and Anti-Fibrosis Effects in Pulmonary Fibrosis Mice

作　　者：徐昌君[1] 方松文 李宏彬[1] 但勇[1] 张川[1] 徐林林[1] 刘杨[1] 张莉莉[2] 杨长福[1] 

机构地区：[1]贵阳中医学院基础医学院,贵阳550002 [2]贵州省人民医院护士学校,贵阳550002

出　　处：《世界科学技术-中医药现代化》2016年第4期646-652,共7页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：国家自然科学基金委地区科学基金项目(81260587):从自噬/溶酶体途径探讨组织蛋白酶D对特发性肺纤维化中II肺泡上皮细胞损伤的的分子机制及加减补肺汤的干预研究;负责人:杨长福;贵州省科技厅科学技术基金(黔科合J字[2014]2034号):miRNA?21;LET?7d对IPF炎症反应及细胞自噬途径的影响;负责人:徐昌君;贵州省高等学校大学生创新创业训练计划:黄芪抗肺纤维化药用成份分析及筛选;负责人:方松文

摘　　要：目的:研究黄芪多糖、黄芪总黄酮、和黄芪总皂苷对博莱霉素(BLM)诱导肺纤维化KM小鼠肺泡炎症影响及抗肺纤化的作用。方法:KM小鼠随机分为假手术组、模型组、药物处理组(黄酮组、多糖组、皂苷组、皂苷+黄酮组)共6组,模型组及药物处理组小鼠气管内一次性滴注BLM,假手术组予等量生理盐水,造模后予相应药物或生理盐水灌胃,第28天取材;分别行肺泡灌洗液细胞计数分类,肺组织HE、Masson染色,免疫组化及western blot测TGF?β1、TNF?α表达水平。结果:1与对照组比较,模型组肺泡灌洗液(BALF)单核细胞和巨噬细胞明显增多(P<0.05),黄芪黄酮治疗组改善较明显,且优于其他成份组(P<0.05);2 Masson结果和HE结果具有高度一致性,炎症反应强度和纤维化程度成正比。黄芪总黄酮能明显改善肺纤维化炎症反应,抑制早期纤维化结节出现,黄芪多糖和黄芪皂苷改善作用不如黄芪黄酮;3模型组TNF?α、TGF?β1免疫组化阳性颗粒明显比对照组增多,与模型组比较,黄芪黄酮能有效降低TNF?α、TGF?β1水平,黄芪多糖组和黄芪皂苷组与模型组比较虽有一定改善,但是效果不如黄芪黄酮;黄芪皂苷+黄酮联合应用无协同作用;4蛋白印迹结果与免疫组化结果具有一致性。结论:黄芪黄酮能有效抑制肺纤维化炎症反应及后期的纤维化过程,该抑制作用与抑制TNF?α、TGF?β1表达具有密切关系。Astragalus was widely used in the TCM treatment of pulmonary inflammation in fibrosis. This study aimed to exam the therapeutic effects of flavonoids, polysaccharides and saponins in astragalus on pulmonary inflammation in bleomycin（BLM） induced fibrosis KM mice model. BLM were administered intratracheally in the model group and the medication group, while the same volume of normal saline in the control group. Mice were sacrificed after astragalus ingredients administration for 28 days. It was found that neutrophile granulocyte and macrophagocyte in bronchoalveolar lavage fluid were significantly increased in the model group（P 〈 0.05）, which were reversed after administration of astragalus flavonoids. The same cell count results were showed both in Masson and HE staining（P 〈 0.05）. And a positive correlation between inflammatory response and pulmonary fibrosis was presented in the study. However, there was no significant change after the treatments of astragalus polysaccharides, saponins and astragalisaponins plus flavonoids. Quantifing analysis of collagen was consistent with that of inflammation. Astragalus saponins and flavonoids both restrained early fibrosis nodules, while astragalus flavone was superior to the astragalus saponin group and the astragalus saponin plus flavone group. TNF-α, TGF-β1 were significantly increased in IHC and western blot results in the model group. Tragalus astragalus flavonoids reversed these trends, which surpassed other ingredients. In conclusion, astragalus flavone and astragalus saponin can inhibit pulmonary inflammation and fibrosis, which may be related to the antiinflammatory effects of TNF-α and TGF-β1.

关 键 词：黄芪糖 黄芪黄酮 黄芪皂苷 肺纤维化 炎症 TNF-A TGF-B1 

分 类 号：R563[医药卫生—呼吸系统]