香青兰总黄酮灌胃对博来霉素诱导大鼠肺纤维化的抑制作用及其机制  

Inhibitory effect and mechanism of total flavonoids of Dracocephalum Moldavica L.on bleomycin-induced pulmonary fibrosis in rats

作　　者：孙小玉 陈丽 高瑞芳 周群明 康嘉桐 于慧[3] 靳敏[1] SUN Xiaoyu;CHEN Li;GAO Ruifang;ZHOU Qunming;KANG Jiatong;YU Hui;JIN Min(School of Public Health,Baotou Medical College,Baotou 014000,China;不详)

机构地区：[1]包头医学院公共卫生学院,内蒙古包头014000 [2]石家庄市裕华区疾病预防控制中心 [3]包头医学院基础医学与法医学院

出　　处：《山东医药》2024年第23期41-46,共6页Shandong Medical Journal

基　　金：国家自然科学基金资助项目(82260092)。

摘　　要：目的观察香青兰总黄酮灌胃对博来霉素诱导大鼠肺纤维化(PF)的影响,并基于肠道菌群和血清代谢组学方法探讨其可能的机制。方法将32只雄性SD大鼠随机分为对照组、模型组、香青兰总黄酮高剂量组及香青兰总黄酮低剂量组,每组8只。除对照组外,其余各组均采用气管内滴入博来霉素的方法建立PF模型;香青兰总黄酮高、低剂量组建模后分别给予香青兰总黄酮400、100 mg/kg灌胃,对照组和模型组分别给予等体积生理盐水灌胃,1次/天,连续21 d。各组末次给药后处死,采用HE染色及Masson染色观察肺组织病理情况,实时荧光定量PCR法检测肺组织胶原蛋白Ⅲ(COLⅢ)、α平滑肌肌动蛋白(α-SMA)mRNA相对表达量,16 S rRNA测序技术进行肠道菌群α、β多样性分析并检测其相对丰度,超高效液相色谱串联质谱分析并筛选血清关键差异代谢产物,并导入京都基因与基因组百科全书(KEGG)进行代谢途径的富集分析。结果与对照组比较,模型组大鼠肺泡结构被破坏,肺泡间隔增宽,炎症细胞浸润明显,肺泡壁变厚,肺泡之间的距离增宽,可见蓝色条索状胶原纤维沉积;与模型组比较,香青兰总黄酮高、低剂量组大鼠上述病理改变减轻。与对照组比较,模型组大鼠肺组织COLⅢ、α-SMA mRNA相对表达量均升高(P均<0.05);与模型组比较,香青兰总黄酮高、低剂量组肺组织COLⅢ、α-SMA mRNA相对表达量均降低(P均<0.05)。α多样性分析结果显示,与对照组比较,模型组、香青兰总黄酮高剂量和香青兰总黄酮低剂量组大鼠肠道菌群Chao1、Ace均升高(P均<0.05)。β多样性分析结果显示,对照组、香青兰总黄酮高剂量和香青兰总黄酮低剂量组大鼠肠道菌群组成接近,与模型组大鼠肠道菌群组成比较均差异明显。在门水平上,与对照组比较,模型组大鼠拟杆菌门相对丰度降低而厚壁菌门/拟杆菌门升高(P均<0.05);与模型组比较,香青兰总Objective To observe the effect of total flavonoids of Dracocephalum Moldavica L.on bleomycin-in⁃duced pulmonary fibrosis(PF)in rats and to explore the possible mechanism based on intestinal flora and serum metabolo⁃mics approaches.Methods Thirty-two male SD rats were randomly divided into the control group,model group,high-dose total flavonoids of Dracocephalum Moldavica L.group and low-dose total flavonoids of Dracocephalum Moldavica L.group,with 8 rats in each group.In addition to the control group,the model was established by intratracheal drip of bleo⁃mycin in each group;400 mg/kg and 100 mg/kg of total flavonoids of Dracocephalum Moldavica L.were given by gavage in the high-and low-dose groups,respectively,and an equal volume of normal saline was given by gavage in the control group and the model group,respectively,once a day for 21 d.The lung histopathology was observed by HE and Masson staining.The collagenⅢ(COLⅢ)andα-smooth muscle actin(α-SMA)mRNA expression levels in the lung tissues were detected by real-time fluorescence quantitative PCR.16S rRNA sequencing technology was used to detect the diversity and relative abundance of intestinal flora,and ultra-high-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)was used to analyse and screen for the key differential metabolites in serum,which were then imported into the Kyoto Encyclopedia of Genes and Genomes(KEGG)for the metabolic pathway enrichment analysis.Results Com⁃pared with the control group,the alveolar structure of rats in the model group was destroyed,the alveolar intervals were widened,the inflammatory cell infiltration was obvious,the alveolar wall was thickened,the distance between the alveoli was widened,and the deposition of collagen fibres in blue stripes was seen;compared with the model group,the above pathological changes were reduced in rats in the high-and low-dose total flavonoids of Dracocephalum Moldavica L.groups.Compared with the control group,the relative expression levels of COLⅢandα-SMA mRNA

关 键 词：香青兰总黄酮 肺纤维化 肠道菌群 代谢组学 AMP活化蛋白激酶 

分 类 号：R285[医药卫生—中药学]