心阳片对缺氧诱导大鼠肺血管重构的影响  

Effects of Xinyang Tablets on Pulmonary Vascular Remodeling of Rats Induced by Hypoxia

作　　者：高安然 李硕 黄婷[1,2] 谭小翠 李劲草[2] 薛瑞 张杨 王萧 张有志 GAO Anran;LI Shuo;HUANG Ting;TAN Xiaocui;LI Jingcao;XUE Rui;ZHANG Yang;WANG Xiao;ZHANG Youzhi(Laboratory Animal Center,Guangzhou University of Chinese Medicine,Guangzhou 510405 Guangdong,China;State Key Laboratory of Toxicology and Medical Countermeasures,Institute of Pharmacology and Toxicology,Academy of Military Medical Sciences,Beijing 100850,China)

机构地区：[1]广州中医药大学动物实验中心,广东广州510405 [2]军事科学院军事医学研究院毒物药物研究所抗毒药物与毒理学国家重点实验室,北京100850

出　　处：《中药新药与临床药理》2022年第10期1328-1337,共10页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：广州市科技计划项目(202002030433);广东省普通高校特色创新项目(2019KTSCX030);广东省基础与应用基础研究基金自然科学基金项目(2021A1515012524)。

摘　　要：目的探讨心阳片(黄芪、红参、淫羊藿等)对缺氧诱导大鼠肺血管重构的影响及其作用机制。方法将雄性SD大鼠随机分为正常组、模型组、心阳片组(270 mg·kg^(-1))和卡托普利组(阳性对照,30 mg·kg^(-1)),每组7只。将大鼠置于全自动低压低氧实验环境舱中,模拟海拔5500 m的气候环境,连续低压缺氧21 d,建立大鼠肺血管重构模型。采用苏木素-伊红(HE)染色法观察各组大鼠肺小动脉血管病理学形态变化,马松(Masson)染色法观察肺组织纤维化程度;蛋白免疫印迹(Western Blot)法测定肺组织肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6蛋白表达水平,酶联免疫吸附法(ELISA)测定肺组织TNF-α、IL-6含量变化;16S rRNA基因测序法检测各组大鼠肠道菌群多样性和菌群组成的变化,并分析肠道菌群与肺血管重构及纤维化之间的相关性。结果与正常组比较,模型组大鼠肺血管壁厚度和肺纤维化面积明显增加(P<0.001,P<0.01);肺组织中TNF-α、IL-6蛋白表达水平(P<0.05)及含量(P<0.001,P<0.01)均明显升高;肠道菌群多样性明显减少(P<0.01),菌群组成发生改变,放线菌、丹毒丝菌及罗姆布茨菌的菌群相对丰度均明显降低(P<0.05)。与模型组比较,心阳片组大鼠肺血管壁厚度和肺纤维化面积明显减小(P<0.01,P<0.05);肺组织中TNF-α、IL-6蛋白表达水平及含量均明显降低(P<0.01);肠道菌群多样性增加(P<0.05),放线菌、丹毒丝菌及罗姆布茨菌的菌群相对丰度均明显升高(分别P<0.05,P<0.01,P<0.05),且丁酸盐产生菌丹毒丝菌的相对丰度与肺血管壁厚度及纤维化程度呈负相关(P<0.01,P<0.05)。结论心阳片能够减轻缺氧诱导的肺血管重构及纤维化程度,其作用机制可能与抑制肺组织炎症,调节肠道菌群多样性及组成,提高丁酸盐产生菌的菌群丰度有关。Objective To investigate the effects and mechanisms of Xinyang Tablets(XYT;Astragali Radix,Ginseng Radix et Rhizoma Rubra, Epimedii Folium, etc)on pulmonary vascular remodeling in rats induced by hypoxia. Methods Male SD rats were randomly divided into control group,model group, XYT group(270 mg ·kg^(-1))and captopril group(positive control,30 mg·kg^(-1)),with 7 rats in each group. Rats were maintained for 21days at the equivalent altitude of 5 500 m in a hypobaric hypoxia chamber to establish pulmonary vascular remodeling model. Pathological morphological changes in the pulmonary vessels were observed by hematoxylin and eosin(HE)staining. The fibrosis of lung tissues was evaluated by Masson staining. Protein expression levels of TNF-α、IL-6 in the lung tissues were measured using Western Blot. The content of TNF-α、IL-6 in the lung tissue was tested by ELISA. The diversity and composition of gut microbiota in rats were detected by 16S rRNA gene sequencing. And we analyzed the association between gut microbiota, pulmonary vascular remodeling and fibrosis in rats induced by hypoxia. Results Compared with control group,the thickness of pulmonary vessel and area of the pulmonary fibrosis in model group were remarkedly increased(P<0.001, P<0.01). The protein expressions(P<0.05) and content levels(P<0.001, P<0.01) of TNF-α、 IL-6 in the lung tissue were obviously increased. The diversity of gut microbiota was decreased(P<0.01)and the composition was changed. The relative abundance of Actinobacteria,Erysipelotrichaceae, and Romboutsia was significantly reduced(P<0.05). Compared with model group, the thickness of pulmonary vessel and area of the pulmonary fibrosis in XYT group were remarkedly reduced(P<0.01,P<0.05). The protein expressions and content levels of TNF-α、IL-6 in the lung tissue were obviously decreased(P<0.01). The diversity of gut microbiota was increased(P<0.05). The relative abundance of Actinobacteria,Erysipelotrichaceae,and Romboutsia was apparently increased(P<0.05,P<0.01,P<0.05). And the a

关 键 词：心阳片 缺氧 肺血管重构 肺纤维化 炎症 肠道菌群 大鼠 

分 类 号：R285.5[医药卫生—中药学]