水栀子对原发性高血压大鼠血压影响的代谢组学研究
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摘要
目的:通过代谢组学方法探讨水栀子对原发性高血压大鼠降压作用的相关机制。方法:基于超高效液相-四级杆串联飞行时间质谱(UHPLC-Q-TOF-MS)技术分析原发性高血压组与水栀子干预组大鼠的尿液样本;利用SIMCA-P 13. 0进行主成分分析(PCA)和正交偏最小二乘判别分析(OPLS-DA),探讨原发性高血压组和水栀子干预组大鼠之间的代谢组学差异,寻找潜在的生物标志物;在通路富集分析的基础上,构建与水栀子降压作用相关的代谢网络。结果:与原发性高血压组相比,水栀子干预组大鼠的血压明显降低,且尿液中17个潜在生物标志物的水平发生显著变化,其中涉及的代谢通路主要有:精氨酸与脯氨酸代谢、肾上腺素(β-肾上腺素受体激动剂/拮抗剂)代谢、牛磺酸和亚牛磺酸代谢。结论:水栀子可通过调节原发性高血压大鼠体内的代谢紊乱而发挥降压作用。
Objective: To explore the role of metabolic intervention in the effect of Gardenia jasminoides var. radicans fruit extract on spontaneously hypertensive rats using metabolomics method. Methods: The urine samples of spontaneously hypertensive rats group and GF extract therapy group were analyzed by UHPLC-Q-TOF-MS.Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were performed by SIMCA-P13. 0 software. Metabolites distinctions between the spontaneously hypertensive mice and the GF extract therapy ones were investigated to find potential biomarkers. A metabolic network related to the antihypertensive effect of GF extract was built. Results: Compared with the spontaneously hypertensive rats group,the blood pressure of the rats in the GF extract therapy group was significantly reduced and 17 endogenous metabolites in the urine of the therapy group significantly changed. The main metabolic pathways were arginine and valine metabolic pathways,epinephrine (β-adrenoceptor agonist/antagonist) metabolism,taurine and metataurine metabolism.Conclusion: The extract of Gardenia jasminoides var. radicans fruit play its antihypertensive effect through improving the metabolic disorders in spontaneously hypertensive rats.
Objective: To explore the role of metabolic intervention in the effect of Gardenia jasminoides var. radicans fruit extract on spontaneously hypertensive rats using metabolomics method. Methods: The urine samples of spontaneously hypertensive rats group and GF extract therapy group were analyzed by UHPLC-Q-TOF-MS.Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were performed by SIMCA-P13. 0 software. Metabolites distinctions between the spontaneously hypertensive mice and the GF extract therapy ones were investigated to find potential biomarkers. A metabolic network related to the antihypertensive effect of GF extract was built. Results: Compared with the spontaneously hypertensive rats group,the blood pressure of the rats in the GF extract therapy group was significantly reduced and 17 endogenous metabolites in the urine of the therapy group significantly changed. The main metabolic pathways were arginine and valine metabolic pathways,epinephrine (β-adrenoceptor agonist/antagonist) metabolism,taurine and metataurine metabolism.Conclusion: The extract of Gardenia jasminoides var. radicans fruit play its antihypertensive effect through improving the metabolic disorders in spontaneously hypertensive rats.
引文
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[18]邹林蓁,蒋海强,周洪雷,等.泽泻在自发性高血压大鼠体内尿液代谢组学的研究[J].中华中医药杂志,2018,33(9):4151-4154.
[19]DELANEY J,NEVILLE WA,SWAIN A,et al.Phenylacetylglycine,a putative biomarker of phospholipidosis:its origins and relevance tophospholipid accumulation using amiodarone treatedrats as a AD[J].Biomarkers,2004,9(3):271-290.
[20]汪晓芬,和渝斌,张源波,等.高血压发病机制及诊疗研究的新认识[J].中国循证心血管医学杂志,2015,7(2):281-282.
[21]张金枝.原发性高血压与肾损害[J].临床心血管病杂志,2004,20(7):385.
[22]曹彦刚.水栀子乙酸乙酯部位化学成分及其生物活性研究[D].黑龙江:黑龙江中医药大学,2018.
[2]杜美玲,杨新春,蔡军.原发性高血压的危险因素和发病机制的新认识[J].诊断学理论与实践,2012,11(6):554-557.
[3]黄体钢.利尿药在抗高血压治疗中的应用及其限度[J].继续医学教育,2006,21(4):299-303.
[4]沙中坚,吴江.各类降压药的副作用及正确应用[J].中国误诊学杂志,2005,5(14):184-185.
[5]田晓伟,马闻.中药利尿药和西药利尿药在高血压中的应用研究[J].中国继续医学教育,2017,9(4):201-203.
[6]覃芳敏.水栀子化学成分研究[D].广州:暨南大学,2014.
[7]周素文,肖文华,周大庆,等.水栀类与山栀类栀子药理作用比较实验[J].中国医院药学杂志,1991,11(2):55-58.
[8]邹林蓁,蒋海强,周洪雷,等.泽泻在自发性高血压大鼠体内尿液代谢组学的研究[J].中华中医药杂志,2018,33(9):4151-4154.
[9]吴力,陈霁虹,葛丹霞,等.桂枝茯苓汤加味对老年原发性高血压血瘀证患者脉压差及血细胞比容的影响[J].中医杂志,2018,59(5):402-405.
[10]王凌玲,雷梦觉,吴小何,等.高血压早期肾损害检测血清胱抑素C、尿微量白蛋白/肌酐比值及内皮素-1的诊断价值[J].实用临床医学,2013,14(2):21-24.
[11]杨波.1-甲脲乙醇酸酐、甲基胍对HK-2细胞的凋亡、纤维化相关因子表达及药物干预的研究[D].长沙:中南大学,2006.
[12]莫喜明,唐爱国.血清肌酸的测定及临床意义[J].实用预防医学,2005,12(6):1522-1523.
[13]孔俭.罗格列酮对自发性高血压病大鼠降压作用和心血管保护作用的研究[D].吉林:吉林大学,2004.
[14]TRACHTMAN H,DEL PR,RAO P,et al.Taurine lowers blood pressure in the spontaneously hypertensive rat by a catecholamine independent mechanism[J].Am J Hypertens,1989,2(12):909-912.
[15]FUJITA T,SATO Y.Hypotensive effect of taurine.Possible involve-ment of the sympathetic nervous system and endogenous opiates[J].J Clin Invest,1988,82(3):993-997.
[16]AZUMA M,TAKAHASHI K,FUKUDA T,et al.Taurine attenuates hypertrophy induced by angiotensin in cultured neonatal rat cardiacmyocytes[J].Eur J Pharmacol,2000,403(3):181-188.
[17]周咏梅,舒燕.原发性高血压合并非糖尿病患者血浆肿瘤坏死因子-α水平变化与胰岛素抵抗的关系[J].实用医院临床杂志,2018,15(5):76-78.
[18]邹林蓁,蒋海强,周洪雷,等.泽泻在自发性高血压大鼠体内尿液代谢组学的研究[J].中华中医药杂志,2018,33(9):4151-4154.
[19]DELANEY J,NEVILLE WA,SWAIN A,et al.Phenylacetylglycine,a putative biomarker of phospholipidosis:its origins and relevance tophospholipid accumulation using amiodarone treatedrats as a AD[J].Biomarkers,2004,9(3):271-290.
[20]汪晓芬,和渝斌,张源波,等.高血压发病机制及诊疗研究的新认识[J].中国循证心血管医学杂志,2015,7(2):281-282.
[21]张金枝.原发性高血压与肾损害[J].临床心血管病杂志,2004,20(7):385.
[22]曹彦刚.水栀子乙酸乙酯部位化学成分及其生物活性研究[D].黑龙江:黑龙江中医药大学,2018.
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