机构地区:[1]深圳北京中医药大学研究院,广东深圳518118 [2]北京中医药大学生命科学学院,北京102488 [3]甘肃中医药大学中医临床学院,甘肃兰州730030
出 处:《中国中药杂志》2023年第5期1319-1329,共11页China Journal of Chinese Materia Medica
基 金:深圳市科技计划项目(JCYJ20210324135410028)。
摘 要:该研究旨在探讨人参茎叶总皂苷对脂多糖(lipopolysaccharide,LPS)诱导的小鼠急性肺损伤(acute lung injury,ALI)的生物学效应及潜在的作用机制。60只雄性C57BL/6J小鼠随机分为正常组,模型组,人参茎叶总皂苷正常给药组(61.65 mg·kg^(-1)),人参茎叶总皂苷低、中、高剂量组(15.4125、30.825、61.65 mg·kg^(-1)),小鼠连续给药1周后开始造模,造模后24 h,处死小鼠获取肺组织,并计算肺湿/干比;观察支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)中炎性细胞数目,检测BALF中白细胞介素-1β(interleukin-1β,IL-1β)、白细胞介素-6(interleukin-6,IL-6)和肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)的水平;检测肺组织中IL-1β、IL-6和TNF-αmRNA的表达水平,以及髓过氧化物酶(myeloperoxidase,MPO)、谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)、超氧化物歧化酶(superoxide dismutase,SOD)和丙二醛(malondialdehyde,MDA)的水平;苏木素-伊红(hematoxylin-eosin,HE)染色观察肺组织病理变化;16S rRNA高通量测序检测小鼠粪便中的肠道菌群;气相色谱-质谱分析检测血清中短链脂肪酸(short-chain fatty acids,SCFAs)的含量。结果显示,人参茎叶总皂苷能降低LPS诱导的ALI小鼠肺系数、肺湿/干比和肺组织损伤,减少BALF中炎性细胞的数量,抑制BALF炎症因子的水平,抑制肺组织中炎症因子mRNA、MPO和MDA的水平,升高肺组织中GSH-Px和SOD的活力;改善ALI小鼠肠道菌群紊乱,恢复肠道菌群的多样性,提升有益菌Lachnospiraceae和Muribaculaceae的相对丰度,降低有害菌Prevotellaceae的相对丰度,提高血清中SCFAs(乙酸、丙酸、丁酸)的含量。上述研究表明人参茎叶总皂苷能通过调节肠道菌群和SCFAs代谢改善ALI小鼠肺组织水肿、炎症反应和氧化应激。This study aimed to investigate the biological effects and underlying mechanisms of the total ginsenosides from Panax ginseng stems and leaves on lipopolysaccharide(LPS)-induced acute lung injury(ALI)in mice.Sixty male C57BL/6J mice were randomly divided into a control group,a model group,the total ginsenosides from P.ginseng stems and leaves normal administration group(61.65 mg·kg^(-1)),and low-,medium-,and high-dose total ginsenosides from P.ginseng stems and leaves groups(15.4125,30.825,and 61.65 mg·kg^(-1)).Mice were administered for seven continuous days before modeling.Twenty-four hours after modeling,mice were sacrificed to obtain lung tissues and calculate lung wet/dry ratio.The number of inflammatory cells in bronchoalveolar lavage fluid(BALF)was detected.The levels of interleukin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)in BALF were detected.The mRNA expression levels of IL-1β,IL-6,and TNF-α,and the levels of myeloperoxidase(MPO),glutathione peroxidase(GSH-Px),superoxide dismutase(SOD),and malondialdehyde(MDA)in lung tissues were determined.Hematoxylin-eosin(HE)staining was used to observe the pathological changes in lung tissues.The gut microbiota was detected by 16S rRNA sequencing,and gas chromatography-mass spectrometry(GC-MS)was applied to detect the content of short-chain fatty acids(SCFAs)in se-rum.The results showed that the total ginsenosides from P.ginseng stems and leaves could reduce lung index,lung wet/dry ratio,and lung damage in LPS-induced ALI mice,decrease the number of inflammatory cells and levels of inflammatory factors in BALF,inhibit the mRNA expression levels of inflammatory factors and levels of MPO and MDA in lung tissues,and potentiate the activity of GSH-Px and SOD in lung tissues.Furthermore,they could also reverse the gut microbiota disorder,restore the diversity of gut microbiota,increase the relative abundance of Lachnospiraceae and Muribaculaceae,decrease the relative abundance of Prevotellaceae,and enhance the content of SCFAs(acetic acid,p
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