益气通脉方对动脉粥样硬化模型小鼠血清代谢组学的影响

Effects of Yiqi Tongmai Recipe on serum metabolomics of atherosclerotic mice

目的:明确益气通脉方对血清代谢及主动脉病理、斑块的影响,探讨益气通脉方防治动脉粥样硬化的可能机制。方法:36只C57/B6J雄性小鼠中正常组6只,给予普通饮食;30只ApoE-/-小鼠随机分为模型组,益气通脉方低、中、高剂量组,阿托伐他汀组各6只,高脂饲养的同时分别以0.9%氯化钠溶液,低、中、高剂量益气通脉方(0.39,0.78,1.56 g·kg^(-1)·d^(-1)),阿托伐他汀(2.6 mg·kg^(-1)·d^(-1))灌胃,12周后采集血清和主动脉。主动脉油红染色观察斑块面积,切片HE染色观察病理改变,血清以液相色谱-质谱联用分析、筛选差异代谢物,富集相关代谢通路。结果:与模型组相比,益气通脉方组主动脉斑块面积减小(P<0.01),血管病理损伤改善;与正常组相比,模型组有21种代谢物改变明显,包括L-酪氨酸、L-脯氨酸等增高,N-乙酰鸟氨酸、肌醇等降低,参与的代谢通路主要为氨基酸和脂肪酸代谢。结论:益气通脉方可延缓动脉粥样硬化进展,作用机制可能与调节氨基酸、脂肪酸代谢有关。

OBJECTIVE To clarify the effects of Yiqi Tongmai Recipe on serum metabolism,aortic pathology and plaque,and explore the possible mechanism of Yiqi Tongmai Recipe in the treatment of atherosclerosis.METHODS Six of 36 C57/B6 J male mice were given normal diet;the rest 30 ApoE-/- gene mice were randomly divided into model group,Yiqi Tongmai Recipe low-,medium-and high-dose groups and atorvastatin group with 6 mice in each group,and respectively fed with 0.9% NaCl solution,0.39,0.78,1.56 g·kg^(-1)·d^(-1)Yiqi Tongmai Recipe,and 2.6 mg·kg^(-1)·d^(-1)atorvastatin.After 12 weeks,serum and aortic tissues of mice in each group were collected for aortic gross oil red staining to observe the aortic plaque area,and HE staining to observe the pathological changes.Liquid chromatography-mass spectrometry was used to analyze metabolic profiles,screen differential metabolites among the groups,and enrich related metabolic pathways.RESULTS In morphology,compared with that in the model group,the aortic plaque area in Yiqi Tongmai Recipe groups was significantly reduced(P<0.01),and the pathological injury of blood vessel was significantly improved.In terms of serum differential metabolites,a total of 21 metabolites in the model group were significantly changed when compared with those in the normal group,including the level increase of L-tyrosine,L-proline and arachidonic acid,the level decrease of N-acetylornithine,myo-inositol and docosahexaenoic acid,etc.The metabolic pathways mainly involved amino acid metabolism and fatty acid metabolism.CONCLUSION Yiqi Tongmai Recipe can delay the progression of atherosclerosis,and the mechanism may be related to the regulation of amino acid metabolism and fatty acid metabolism.