基于16S rDNA高通量测序探讨山豆根致大鼠肾毒性的肠道菌群变化  

Changes of gut microbiota in rats with nephrotoxicity induced by Sophorae tonkinensis radix et rhizoma based on 16S rDNA sequencing

作　　者：刘畅 何倩倩 尹志刚 王馨悦 骆江利 牛梦伟 周英 LIU Chang;HE Qianqian;YIN Zhigang;WANG Xinyue;LUO Jiangli;NIU Mengwei;ZHOU Ying(School of Pharmacy,Guizhou University of Traditional Chinese Medicine,Guiyang,Guizhou 550025,China;不详)

机构地区：[1]贵州中医药大学药学院,贵州贵阳550025 [2]湘南学院基础医学院

出　　处：《中国微生态学杂志》2025年第2期125-132,共8页Chinese Journal of Microecology

基　　金：贵州省高层次创新型人才(黔科合平台人才—GCC[2023]047);贵州省教育厅2023年度自然科学研究项目(黔教技[2023]069号);贵州省“十四五”中医药、民族医药重点学科[QZYYZDXK(JS)-2021-03]。

摘　　要：目的探究山豆根致大鼠肾毒性的肠道菌群变化,从肠道菌群的角度揭示山豆根的毒性作用机制。方法基于课题组前期建立的山豆根致肾毒性模型,在此基础上,采用16S rDNA测序技术检测对照组、山豆根高中低剂量组大鼠肠道菌群,通过alpha多样性、beta多样性和LEfSe分析等,评价菌群结构的丰富度和多样性的变化;相关性分析探讨大鼠血清中肾损伤相关指标BUN、SCr的水平与菌群的关联性。结果不同剂量山豆根干预后与对照组相比,大鼠的肠道菌群结构发生变化。与对照组相比,山豆根高剂量组的梭状芽胞杆菌属、Paeniclostridium和不动杆菌属的相对丰度增加,乳杆菌属、普雷沃菌属、嗜血杆菌属的相对丰度减少。利用LEfSe分析挖掘差异菌属,与对照组相比,山豆根高剂量组梭状芽胞杆菌属丰度增加。由菌群与炎症因子的关联性分析看出Paeniclostridium、梭状芽胞杆菌属、不动杆菌属可能是高剂量山豆根导致肾损伤的标志菌属。结论山豆根致肾毒性呈剂量依赖性,高剂量山豆根可能通过改变了肠道菌群的多样性,降低了有益菌的丰度和提高有害菌群丰度导致了大鼠肾脏损伤,肠道菌群是山豆根发挥毒性效应的潜在“靶点”。Objective To observe the changes in intestinal microbiota caused by nephrotoxicity in rats and elucidate the toxic mechanism of Sophorae tonkinensis radix et rhizoma(ST)from the perspective of intestinal microbiota.Methods Based on the ST-induced nephrotoxicity model established by the research team,16S rDNA sequencing technology was employed to detect the intestinal microbiota in rats in the control group and the high-,medium-and low-dose groups.The richness and diversity of microbial structure were assessed through alpha diversity,beta diversity and LEfSe analysis.Correlation analysis was conducted between the levels of renal injury-related markers in serum(BUN and SCr)and the microbiota of rats.Results Compared to the control group,the structure of intestinal microbiota of rats altered after exposure to different doses of ST.In the high-dose group,there was an increase in the relative abundance of Clostridium,Paeniclostridium and Acinetobacter genus,while a decrease was observed for Lactobacillus,Prevotella and Haemophilus genus.LEfSe analysis revealed a higher abundance of Clostridium genus in the high-dose group compared to the control.Correlation analysis with inflammatory factors indicated that Paeniclostridium,Clostridium and Acinetobacter might serve as marker bacteria for kidney injury caused by high doses of ST.Conclusion The nephrotoxicity of ST is dose-dependent,with high doses potentially leading to kidney damage in rats by altering the diversity of intestinal microbiota,reducing the abundance of beneficial bacteria,and increasing that of harmful bacteria.The intestinal microbiota is a potential target for the toxic effects of ST.

关 键 词：山豆根 肠道菌群 肾损伤 高通量测序 梭状芽胞杆菌 

分 类 号：R285.5[医药卫生—中药学]