基于非靶向代谢组学的高脂血症大鼠肝脏和血清脂代谢异常相关生物标志物发现及人参皂苷Rb_(1)干预机制研究  

Discovery of biomarkers related to abnormal lipid metabolism in liver and serum and intervention mechanism of ginsenoside Rb_(1) in hyperlipidemia rats based on non-targeted metabolomics

作　　者：冷雪[1] 马艺鑫 LENG Xue;MA Yi-xin(College of Integrated Chinese and Western Medicine,Liaoning University of Traditional Chinese Medicine,Shenyang 110847,China;Key Laboratory of Ministry of Education for Traditional Chinese Medicine Viscera-State Theory and Applications,Liaoning University of Traditional Chinese Medicine,Shenyang 110847,China)

机构地区：[1]辽宁中医药大学中西医结合学院,辽宁沈阳110847 [2]辽宁中医药大学,中医脏象理论及应用教育部重点实验室,辽宁沈阳110847

出　　处：《中国中药杂志》2023年第14期3922-3933,共12页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金青年基金项目(82104552);辽宁省自然科学基金指导计划博士启动基金项目(2020-BS-166)。

摘　　要：通过对高脂血症大鼠肝脏及血清内源性物质进行非靶向代谢组学研究,发现高脂血症大鼠脂代谢异常的相关生物标志物,并探寻人参皂苷Rb_(1)(ginsenoside Rb_(1))改善高脂血症的作用靶点并阐明其作用机制。全自动生化仪检测各组大鼠血清内生化指标含量;通过液相色谱-质谱联用技术(HPLC-MS)对大鼠的肝脏组织和血清代谢质谱进行分析,利用主成分分析(PCA)、正交偏最小二乘法判别分析(OPLS-DA)对比正常组、高脂血症组、人参皂苷Rb_(1)组的代谢数据,筛选潜在的生物标志物,并进一步通过KEGG数据库分析构建相关代谢通路。结果表明高脂引起大鼠血脂紊乱,而人参皂苷Rb_(1)治疗缓解了大鼠血脂紊乱情况;非靶向代谢组学结果显示高脂血症大鼠肝组织中含有297种差异代谢物,血清样本中含有294种差异代谢物,人参皂苷Rb_(1)干预高脂血症大鼠的差异性代谢物共有560种,其中回调肝脏和血清样本共同代谢物是紫苏酸(perillic acid)和N-鸟氨酰基-L-牛磺酸(N-ornithyl-L-taurine),二者可作为人参皂苷Rb_(1)改善高脂血症的潜在生物标志物;通过对其肝脏和血清的通路富集发现人参皂苷Rb_(1)可以共同参与肝脏和血清中胆碱代谢通路,此外还通过参与ABC转运蛋白,丙氨酸、天冬氨酸与谷氨酸代谢,蛋白质消化和吸收,β-丙氨酸代谢,牛磺酸和亚牛磺酸代谢,咖啡因代谢,缬氨酸、亮氨酸和异亮氨酸生物合成,花生四烯酸代谢,蛋氨酸及半胱氨酸代谢等10条通路改善大鼠血脂紊乱。Through the non-targeted metabolomics study of endogenous substances in the liver and serum of hyperlipidemia rats,the biomarkers related to abnormal lipid metabolism in hyperlipidemia rats were found,and the target of ginsenoside Rb_(1) in improving hyperlipidemia was explored and its mechanism was elucidated.The content of serum biochemical indexes of rats in each group was detected by the automatic biochemical analyzer.The metabolite profiles of liver tissues and serum of rats were analyzed by HPLC-MS.Principal component analysis(PCA)and orthogonal partial least squares-discriminant analysis(OPLS-DA)were used to compare and analyze the metabolic data in the normal group,the hyperlipidemia group,and the ginsenoside Rb_(1) group,and screen potential biomar-kers.The related metabolic pathways were further constructed by KEGG database analysis.The results showed that hyperlipemia induced dyslipidemia in rats,which was alleviated by ginsenoside Rb_(1).The non-targeted metabolomics results showed that there were 297 differential metabolites in the liver tissues of hyperlipidemia rats,294 differential metabolites in the serum samples,and 560 diffe-rential metabolites in the hyperlipidemia rats treated by ginsenoside Rb_(1).Perillic acid and N-ornithyl-L-taurine were common metabolites in the liver and serum samples,which could be used as potential biomarkers for ginsenoside Rb_(1) in the improvement of hyperlipidemia.As revealed by pathway enrichment in the liver and serum,ginsenoside Rb_(1) could participate in the metabolic pathway of choline in both the liver and serum.In addition,ginsenoside Rb_(1) also participated in the ABC transporter,alanine,aspartic acid,and glutamate metabolism,protein digestion and absorption,β-alanine metabolism,taurine and hypotaurine metabolism,caffeine metabolism,valine,leucine,and isoleucine biosynthesis,arachidonic acid metabolism,and methionine and cysteine metabolism to improve dyslipidemia in rats.

关 键 词：人参皂苷Rb_(1) 非靶向代谢组学 高脂血症 血清 肝脏 

分 类 号：R285.5[医药卫生—中药学]