益气通脉方干预动脉粥样硬化模型小鼠血清氨基酸代谢的变化  

Effects of Yiqi Tongmai Fang on serum amino acid metabolism of atherosclerotic mice

作　　者：王姝瑞 张翌蕾 焦伟杰 刘志华[3] 张奎明[1,2] 崔应麟 Wang Shurui;Zhang Yilei;Jiao Weijie;Liu Zhihua;Zhang Kuiming;Cui Yinglin(Second Clinical School,Henan University of Chinese Medicine,Zhengzhou 450046,Henan Province,China;Henan Key Laboratory of Chinese Medicine for Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases,Zhengzhou 450002,Henan Province,China;Henan Hospital of Chinese Medicine,Zhengzhou 450002,Henan Province,China)

机构地区：[1]河南中医药大学第二临床医学院,河南省郑州市450046 [2]河南省中医药防治心脑血管病重点实验室,河南省郑州市450002 [3]河南省中医院,河南省郑州市450002

出　　处：《中国组织工程研究》2023年第28期4441-4447,共7页Chinese Journal of Tissue Engineering Research

基　　金：河南省科技攻关项目(212102311123),项目负责人:崔应麟;河南省科技攻关项目(212102311139),项目负责人:刘志华。

摘　　要：背景:动脉粥样硬化是多种心脑血管疾病的病理基础。益气通脉方能显著改善患者动脉粥样硬化,然而关于动脉粥样硬化及益气通脉方干预下的代谢谱及机制分析尚不完善。目的:探讨益气通脉方治疗动脉粥样硬化的可能作用机制。方法:选取36只C57/B6J雄性小鼠,其中正常组6只,给予普通饮食12周;其余30只ApoE^(-/-)基因小鼠随机分为模型组、益气通脉方低、中、高剂量组和阿托伐他汀组,每组6只,高脂饲养的同时分别以氯化钠、低、中、高剂量益气通脉方[0.39,0.78,1.56 g/(kg·d)]及阿托伐他汀2.6 mg/(kg·d)灌胃,12周后采集各组小鼠血清和主动脉组织。通过血管组织病理切片观察各组小鼠主动脉病理改变程度与血管狭窄情况,血清采用超高效液相色谱-质谱高通量靶标代谢组学技术分析代谢谱,筛选组间差异氨基酸。结果与结论:(1)在形态上,与模型组相比,益气通脉方各组血管病理损伤和狭窄程度明显改善;(2)在血清氨基酸代谢上,与正常组相比,模型组共有7种氨基酸水平明显改变,包括L-谷氨酸、L-酪氨酸、L-天冬氨酸、L-赖氨酸、L-缬氨酸水平的升高,L-精氨酸、3-甲基-L-组氨酸水平的降低;(3)益气通脉方能够调节差异氨基酸水平,并且益气通脉方高剂量组调节代谢物最多;(4)提示益气通脉方可延缓动脉粥样硬化进展,其中益气通脉方高剂量组作用最为显著,作用机制可能与调节氨基酸代谢相关。BACKGROUND:Atherosclerosis is the pathological basis of many cardiovascular and cerebrovascular diseases.Yiqi Tongmai Fang can significantly improve atherosclerosis in patients,but the metabolic spectrum and mechanism underlying the intervention of atherosclerosis using Yiqi Tongmai Fang are still incomplete.OBJECTIVE:To explore the possible mechanism of Yiqi Tongmai Fang in the treatment of atherosclerosis.METHODS:Thirty-six male C57/B6J mice were selected,6 of which were used as normal controls and given normal diet for 12 weeks.The remaining 30 ApoE^(-/-)mice were randomly divided into model group,low-,medium-and high-dose Yiqi Tongmai Fang groups and atorvastatin group,with 6 mice in each group,and then were fed with high fat diet combine with intragastrical administration of sodium chloride,low-,medium-and high-dose Yiqi Tongmai Fang(0.39,0.78,1.56 g/kg per day)and atorvastatin(2.6 mg/kg per day),respectively.Serum and aortic tissue were collected after 12 weeks.The pathological changes of the aorta and vascular stenosis were observed by vascular histopathological section.The serum samples were analyzed by ultrahigh performance liquid chromatography-mass spectrometer for high-throughput target metabolomics,to screen different amino acids between groups.RESULTS AND CONCLUSION:In terms of morphology,vascular pathological injury and stenosis were significantly improved in the Yiqi Tongmai Fang groups compared with the model group.In terms of serum amino acid metabolism,the levels of seven amino acids were significantly changed in the Yiqi Tongmai Fang group compared with the normal control group,including the increased levels of L-Glutamic acid,L-Tyrosine,L-Aspartate,L-Lysine and L-Valine,and the decreased levels of L-Arginine and 3-methyl-L-histidine.Yiqi Tongmai Fang could regulate the levels of different amino acids and high-dose Yiqi Tongmai Fang could regulate the most metabolites.Overall,these findings indicate that Yiqi Tongmai Fang can delay the progression of atherosclerosis and its mechanism may be re

关 键 词：益气通脉方 动脉粥样硬化 氨基酸代谢 ApoE^(-/-)小鼠 超高效液相色谱-质谱 

分 类 号：R459.9[医药卫生—治疗学] R318[医药卫生—临床医学] R543