基于肠道菌群和代谢组学探讨黄芩多糖对COPD大鼠的治疗作用  

Therapeutic effect of Scutellaria baicalensis polysaccharide on rats with chronic obstructive pulmonary disease based on gut microbiota and metabolomics

作　　者：叶苗云 白光剑 俞莉 王雅琪 杨明 YE Miaoyun;BAI Guangjian;YU Li;WANG Yaqi;YANG Ming(State Key Laboratory of Innovation Drug and Efficient Energy-Saving Pharmaceutical Equipment,Jiangxi University of Chinese Medicine,Jiangxi Nanchang 330004,China)

机构地区：[1]江西中医药大学现代中药制剂教育部重点实验室,江西南昌330004

出　　处：《中国医院药学杂志》2025年第4期387-395,共9页Chinese Journal of Hospital Pharmacy

基　　金：国家自然科学基金项目(编号:82260762);2023年江西省大学生创新创业训练计划项目(编号:X202310412170)。

摘　　要：目的:考察黄芩多糖对慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)大鼠肠道菌群和内源性代谢物的影响,探讨黄芩多糖治疗肺部疾病作用机制。方法:采用烟熏方式复制大鼠COPD模型,观察肺功能、组织病理、肺组织中炎症和紧密连接蛋白水平,以及血管重构因子变化情况,评价黄芩多糖疗效。采用16S rRNA测序和超高效液相色谱-串联质谱法(UPLC-MS/MS)检测大鼠肠道菌群和代谢物的变化,Spearman进行肠道菌群与代谢组学之间的关联分析。结果:与模型组比较,黄芩多糖显著提高大鼠肺功能(P<0.05),明显改善肺、肠道和气管组织损伤,减少血管重构及气道重塑,降低IL-6、TNF-α mRNA表达水平(P<0.01),提高Claudin、Occludin mRNA表达水平(P<0.01)。16S rRNA测序结果表明,黄芩多糖可以极显著增加Treponema、Lactobacillus、Muribaculaceae和Romboutsia丰度(P<0.01)。粪便代谢组学结果显示,黄芩多糖通过影响苯丙氨酸代谢和苯丙氨酸、酪氨酸和色氨酸生物合成通路缓解肺部疾病。Spearman结果表明UCG-005属丰度与色氨酸、吲哚氨酸代谢物水平呈负相关趋势。结论:黄芩多糖改善COPD的作用机制可能与调控肠道菌群组成和苯丙氨酸代谢以及苯丙氨酸、酪氨酸和色氨酸生物合成通路有关。OBJECTIVE To investigate the effects of Scutellaria baicalensis polysaccharides on the gut microbiota and endogenous metabolites in rats with chronic obstructive pulmonary disease(COPD),and to explore the mechanism of Scutellaria baicalensis polysaccharides in treating lung diseases.METHODS The COPD model in rats was created by exposure to cigarette smoking,and the therapeutic effect of Scutellaria baicalensis polysaccharides was evaluated through examining lung function,histopathology,inflammation and tight junction protein levels in lung tissue,as well as changes in vascular remodeling factors.Using 16S rRNA sequencing and ultra-high-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS),changes in rat gut microbiota and metabolites were detected.Spearman correlation analysis was performed to identify the relationship between gut microbiota and metabolomics in COPD rats.RESULTS Compared with the model group,Scutellaria baicalensis polysaccharides significantly improved lung function in COPD rats(P<0.05),and alleviated lung,intestinal,and tracheal tissue damages,reduced vascular remodeling and airway remodeling,and decreased mRNA levels of IL-6 and TNF-α(P<0.01),but increased mRNA levels of Claudin and Occludin(P<0.01).The 16S rRNA sequencing results showed that Scutellaria baicalensis polysaccharides could significantly increase the abundances of Treponema,Lactobacillus,Muriaculaceae,and Romboutsia(P<0.01).Fecal metabolomics results showed that Scutellaria baicalensis polysaccharides alleviated lung diseases by affecting phenylalanine metabolism and the biosynthesis pathways of phenylalanine,tyrosine,and tryptophan.Spearman correlation analysis showed that the abundance of UCG-005 was negatively correlated with the levels of metabolites tryptophan and indoleline.CONCLUSION Scutellaria bacalensis polysacharide relieves COPD by regulating the intestinal microbiota composition and phenylalanine metabolism,as well as the phenylalanine,tyrosine and tryptophan biosynthesis pathways.

关 键 词：黄芩多糖 慢性阻塞性肺疾病 肠道菌群 粪便代谢组学 

分 类 号：R282[医药卫生—中药学] R966[医药卫生—中医学]