基于肠道菌群及代谢组学探讨胆南星的降血脂作用机制  

Hypolipidemic effect and mechanism of Arisaema Cum Bile based on gut microbiota and metabolomics

作　　者：张澎 苏发智 朱恩琳 白晨曦 张宝武 孙延平[1] 匡海学[1] 王秋红[1,2] ZHANG Peng;SU Fa-zhi;ZHU En-lin;BAI Chen-xi;ZHANG Bao-wu;SUN Yan-ping;KUANG Hai-xue;WANG Qiu-hong(Key Laboratory of Basic and Application Research of Beiyao,Ministry of Education,Heilongjiang University of Chinese Medicine,Harbin 150040,China;Department of Chinese Materia Medica Processing,School of Traditional Chinese Medicine,Guangdong Pharmaceutical University,Guangzhou 510006,China;Clinical Medical College of Acupuncture Moxibustion and Rehabilitation,Guangzhou University of Chinese Medicine,Guangzhou 510006,China)

机构地区：[1]黑龙江中医药大学教育部北药基础与应用研究重点实验室,黑龙江哈尔滨150040 [2]广东药科大学中药学院中药炮制学教研室,广东广州510006 [3]广州中医药大学针灸康复临床医学院,广东广州510006

出　　处：《中国中药杂志》2025年第6期1544-1557,共14页China Journal of Chinese Materia Medica

基　　金：2022年全国名老中医药专家传承工作室建设项目(国中医药人教函[2022]75号);第七批全国老中医药专家学术经验继承工作项目(国中医药人教函[2022]76号);黑龙江省“头雁”团队支持项目(黑龙江省头雁行动领导小组文件[2019]5号);国家中医药管理局中医药传承与创新“百千万”人才工程-岐黄工程首席科学家支持项目(国中医药人教函[2021]7号)。

摘　　要：基于高脂饮食诱导的高脂血症大鼠模型组,评价胆南星的降脂作用并探讨其作用机制,以期为胆南星的临床应用提供实验依据。该研究采用生化分析法检测大鼠血清中丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、甘油三酯(TG)、总胆固醇(TC)水平评价胆南星的降脂活性;并采用16S rDNA测序及代谢组学技术,共同阐释胆南星的降血脂作用机制。实验结果表明,给予高剂量胆南星(PBA-H)能够显著降低模型组大鼠血清中的ALT、AST、LDL-C、TG、TC含量(P<0.01),显著升高HDL-C的含量(P<0.01),该作用与非诺贝特的作用趋势相同,并无显著性差异。此外,胆南星能显著减轻肝细胞气球样变性,缓解脂肪变性程度。16S rDNA结果表明,PBA-H明显增强模型组大鼠肠道菌群alpha多样性和beta多样性,显著增加Akkermansia菌、Subdoligranulum菌的相对丰度(P<0.01)。肝脏代谢组学分析阐明,PBA-H主要调节花生四烯酸代谢、维生素B6代谢、类固醇激素的生物合成等途径。综上所述,胆南星可显著改善高脂饮食诱导的血脂水平异常及肝脏病变,调节肝脏代谢紊乱,并改善肠道菌群丰度及结构组成,从而发挥降血脂作用,该研究的发现为胆南星的临床应用及高脂血症的治疗提供了实验依据。Based on the high-fat diet-induced hyperlipidemia rat model,this study aimed to evaluate the lipid-lowering effect of Arisaema Cum Bile and explore its mechanisms,providing experimental evidence for its clinical application.Biochemical analysis was used to detect serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),triglycerides(TG),and total cholesterol(TC)to assess the lipid-lowering activity of Arisaema Cum Bile.Additionally,16S rDNA sequencing and metabolomics techniques were employed to jointly elucidate the lipid-lowering mechanisms of Arisaema Cum Bile.The experimental results showed that high-dose Arisaema Cum Bile(PBA-H)significantly reduced serum ALT,AST,LDL-C,TG,and TC levels(P<0.01),and significantly increased HDL-C levels(P<0.01).The effect was similar to that of fenofibrate,with no significant difference.Furthermore,Arisaema Cum Bile significantly alleviated hepatocyte ballooning and mitigated fatty degeneration in liver tissues.As indicated by 16S rDNA sequencing results,PBA-H significantly enhanced both alpha and beta diversity of the gut microbiota in the model rats,notably increasing the relative abundance of Akkermansia and Subdoligranulum species(P<0.01).Liver metabolomics analysis revealed that PBA-H primarily regulated pathways involved in arachidonic acid metabolism,vitamin B_6 metabolism,and steroid biosynthesis.In summary,Arisaema Cum Bile significantly improved abnormal blood lipid levels and liver pathology induced by a high-fat diet,regulated hepatic metabolic disorders,and improved the abundance and structural composition of gut microbiota,thereby exerting its lipid-lowering effect.The findings of this study provide experimental evidence for the clinical application of Arisaema Cum Bile and the treatment of hyperlipidemia.

关 键 词：胆南星 高脂血症 降血脂作用 肠道菌群 代谢组学 

分 类 号：R285.5[医药卫生—中药学]