基于肠道菌群及胆汁酸代谢探讨痰瘀同治优化方抗动脉粥样硬化作用机制  

Exploration of the Mechanism of Anti-atherosclerosis Effect of Optimized Tanyu Tongzhi Decoction Based on Intestinal Flora and Bile Acid Metabolism

作　　者：李盈盈 李若琪 吴浩南 李想 唐丹丽[1] LI Yingying;LI Ruoqi;WU Haonan;LI Xiang;TANG Danli(Experimental Research Center,China Academy of Chinese Medical Sciences,Beijing 100700,China;Institute of Basic Theory for Chinese Medicine,China Academy of Chinese Medical Sciences,Beijing 100700,China)

机构地区：[1]中国中医科学院医学实验中心,北京100700 [2]中国中医科学院中医基础理论研究所,北京100700

出　　处：《中国中医基础医学杂志》2025年第3期449-455,共7页JOURNAL OF BASIC CHINESE MEDICINE

基　　金：国家自然科学基金面上项目(81973722);中国中医科学院科技创新工程项目(CI2021A00604);中国中医科学院科技创新工程项目中医理论传承与创新专项(KYG-202404)。

摘　　要：目的基于肠道菌群及胆汁酸代谢调控探讨痰瘀同治优化方对动脉粥样硬化(atherosclerosis,AS)小鼠的药效及作用机制。方法高脂饮食饲养ApoE^(-/-)小鼠12周构建AS模型,随机分为模型组,痰瘀同治优化方低(6.5g·kg^(-1)·d^(-1))、高(13g·kg^(-1)·d^(-1))剂量组,普食饲养作为对照组。采用生化试剂盒检测血脂水平,HE和油红O染色评价主动脉AS斑块病变程度,ELISA检测血清炎症因子水平,16Sr RNA检测肠道菌群组成,靶向代谢组学分析血清胆汁酸含量。结果与对照组比较,模型组小鼠血清甘油三酯(TG)、总胆固醇(TC)和低密度脂蛋白胆固醇(LDL-C)水平显著上升(P<0.05),高密度脂蛋白胆固醇(HDL-C)水平显著下降(P<0.01),主动脉AS斑块面积显著增大,血清白介素(IL)-1β和肿瘤坏死因子(TNF)-α水平显著上升(P<0.01),肠道菌群Firmicutes/Bacteroidota比值显著升高(P<0.01),差异菌属共96种,其中Escherichia-Shigella等丰度显著上升(P<0.05),Muribaculaceae等丰度显著下降(P<0.01),血清胆汁酸β-鼠胆酸(β-MCA)、鹅去氧胆酸(CDCA)、石胆酸(LCA)水平显著上升(P<0.01)。与模型组比较,痰瘀同治优化方低、高剂量组小鼠TG、TC水平显著下降(P<0.05),主动脉AS斑块面积明显减小,血清IL-1β和TNF-α水平显著下降(P<0.01);痰瘀同治方高剂量组小鼠LDL-C水平显著下降(P<0.01),肠道Firmicutes/Bacteroidota比值显著降低(P<0.01),Escherichia-Shigella等丰度显著下降(P<0.05),Muribaculaceae等丰度显著回升(P<0.05),血清CDCA、LCA水平显著降低(P<0.01)。结论痰瘀同治优化方能够改善高脂饮食诱导的AS,其作用机制与调节肠道菌群组成及胆汁酸代谢密切相关。Objective To explore the efficacy and mechanism of optimized Tanyu Tongzhi decoction(TYTZD)in atherosclerosis(AS)mice based on the regulation of intestinal flora and bile acid metabolism.Methods ApoE^(-/-)mice were fed a high-fat diet for 12 weeks to establish an AS model,while the mice were randomly divided into the model group,TYTZD-L group(6.5 g·kg^(-1)·d^(-1))and TYTZD-H group(13 g·kg^(-1)·d^(-1)).Mice of control group were fed a standard diet.Biochemical assay kits were used to detect serum lipid levels.HE and oil red O staining were used to evaluate the degree of atherosclerotic plaque lesions in the aorta.ELISA was used to detect serum inflammatory factor levels.16S rRNA was used to detect gut microbiota composition,and targeted metabolomics was used to analyze serum bile acid content.Results Compared with the control group,the levels of serum TG,TC,and LDL-C in the model group significantly increased(P<0.05),while the level of HDL-C significantly decreased(P<0.01).The plaque area at the aortic root significantly increased.The levels of serum IL-1βand TNF-αsignificantly increased(P<0.01).In addition,the ratio of intestinal Firmicutes/Bacteroidota significantly increased(P<0.01).There were a total of 96 different bacterial genera,among them,the abundance of Escherichia-Shigella,etc.significantly increased(P<0.05),while the abundance of Muribaculaceae,etc.significantly decreased(P<0.01).Notably,the levels of serumβ-MCA,CDCA,and LCA significantly increased(P<0.01).Compared with the model group,the TYTZD-L group and TYTZD-H group showed significantly reduced levels of TG and TC(P<0.05),decreased area of aortic AS plaques,and significantly lower serum levels of IL-1βand TNF-α(P<0.01).In the TYTZD-H group,the LDL-C level was significantly reduced(P<0.01),the Firmicutes/Bacteroidota ratio in the gut was significantly decreased(P<0.01),the abundance of Escherichia-Shigella,etc.was significantly reduced(P<0.05),the abundance of Muribaculaceae,etc.was significantly increased(P<0.05),and the serum levels of

关 键 词：痰瘀同治优化方 动脉粥样硬化 肠道菌群 胆汁酸代谢 

分 类 号：R285[医药卫生—中药学]