基于代谢组学研究清达颗粒减轻高血压所致心脏损伤的生物学机制  

Biological Mechanism of Qingda Granule on Attenuating Hypertensive Cardiac Injury Based on Metabonomics

作　　者：陈晓萍 程瑛 刘慧馨 沈阿灵 褚剑锋[1,2,3] 谢秋容 杨燕燕[4] 彭军 CHEN Xiaoping;CHENG Ying;LIU Huixin;SHEN Aling;CHU Jianfeng;XIE Qiurong;YANG Yanyan;PENG Jun(Academy of Integrative Medicine,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China;Fujian Key Laboratory of Integrative Medicine on Geriatrics,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China;CHEN Keji Academic Thought Inheritance Studio,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China;Laboratory Animal Center,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China)

机构地区：[1]福建中医药大学中西医结合研究院,福州350122 [2]福建省中西医结合老年性疾病重点实验室,福州350122 [3]福建中医药大学陈可冀学术思想传承工作室,福州350122 [4]福建中医药大学实验动物中心,福州350122

出　　处：《中国中医基础医学杂志》2023年第1期79-85,182,共8页JOURNAL OF BASIC CHINESE MEDICINE

基　　金：国家自然科学基金面上项目(82074363,81774135);福建省社会发展科技重大专项(2019 YZ014004);福建中医药大学陈可冀中西医结合发展基金(CKJ2020003);福建中医药大学高层次人才科研启动资金项目(X2020004-人才)。

摘　　要：目的 探讨清达颗粒对高血压小鼠的血压、心脏损伤的影响,并通过代谢组学技术探讨其对心脏组织代谢的影响。方法 15只10周龄雄性C57BL/6小鼠随机分为对照组、模型组和清达颗粒组各5只,模型和清达颗粒组给予血管紧张素Ⅱ(angiotensin Ⅱ,Ang Ⅱ)埋泵(500 ng/kg/min),并分别给予生理盐水和清达颗粒溶液(1.145 g/kg/d)灌胃;对照组给予生理盐水埋泵及等体积生理盐水灌胃共2周,采用无创血压仪监测小鼠血压,采用小动物超声仪检测小鼠心脏功能,采用HE染色法观察小鼠心脏组织形态的改变,采用非靶向超高效液相色谱-串联质谱技术分析清达颗粒干预对模型小鼠心脏差异代谢产物及对相关通路的影响。结果 与对照组相比较,模型组小鼠的收缩压、舒张压及平均动脉压均显著升高,而清达颗粒干预后均显著降低。与对照组相比较,模型组小鼠心脏的射血分数和左室短轴缩短率均显著降低,而清达颗粒干预后均得到明显改善,模型组小鼠的心肌细胞排列紊乱,清达颗粒干预后心肌细胞排列较为规则。代谢组学检测分析显示,清达颗粒干预能够显著缓解Ang II诱导的小鼠心脏组织内腺嘌呤、组氨酸等代谢产物的改变,且基于代谢差异代谢产物的通路分析发现,清达颗粒干预后嘌呤代谢、苯丙氨酸代谢和亚油酸代谢等信号通路显著被富集。结论 清达颗粒干预能够显著缓解Ang Ⅱ诱导的小鼠血压的升高和心脏功能降低及心脏组织病理改变,通过调控心脏组织苯丙氨酸、嘌呤和亚油酸等代谢通路及相关代谢产物表达,可能是其发挥心脏保护作用机制之一。Objective To explore the effect of Qingda granule(QDG) on angiotensin Ⅱ(Ang Ⅱ)-induced hypertension, cardiac injury and the underlying possible metabolic mechanism using metabonomics technology. Methods 10-week-old male C57BL/6 mice(n= 15) were randomly divided into the control, Ang Ⅱ and Ang Ⅱ+QDG groups(n= 5 for each group). Mice in Ang Ⅱ and Ang Ⅱ+QDG groups were infused with Ang Ⅱ(500 ng/kg/min), and orally administrated with saline or 1. 145 g/kg/d of QDG, while mice in the control group were infused with saline and orally administrated with an equal volume of saline for 2 weeks. The blood pressure was monitored using CODATM noninvasive blood pressure system. The cardiac function was determined by echocardiography. HE staining was performed to observe the pathological change of cardiac tissue. Liquid chromatography tandem mass spectrometry was used to identify the different metabolic profiles and the enriched metabolic pathways. Results The monitor of blood pressure showed that systolic blood pressure(SBP), diastolic blood pressure(DBP) and mean arterial pressure(MAP) of mice were significantly increased in the Ang Ⅱ group compared with the control group, while were attenuated after QDG treatment. Echocardiography showed that the left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS) were significantly decreased in the AngⅡ group compared with the control group, while were alleviated after QDG treatment. HE staining showed that the arrangement of myocardial cells was disordered in the AngⅡ group, while arranged neatly after QDG treatment.Metabonomics analysis showed that QDG treatment could significantly reverse the changes of adenine and histidine in the cardiac tissue in Ang Ⅱ-induced mice, and enriched multiple signaling pathways,including purine metabolism, phenylalanine metabolism, and linoleic acid metabolism. Conclusion QDG treatment attenuated the elevation of blood pressure, and improved cardiac dysfunction and pathological changes in Ang Ⅱ-

关 键 词：清达颗粒 血管紧张素Ⅱ 高血压 代谢组学 

分 类 号：R587.1[医药卫生—内分泌]