益气凉血生肌方与阿托伐他汀片对腹主动脉球囊损伤模型大鼠血管损伤及血清代谢物差异的影响比较研究  

Comparative Study on Effect of Yiqi Liangxue Shengji Formula(益气凉血生肌方)and Atorvastatin Tablets on Vascular Injury and Differences in Serum Metabolites in Abdominal Aortic Balloon Injury Model Rats

作　　者：毛天诗 谢龙 高群 潘熠 贾文浩 林谦[1] MAO Tianshi;XIE Long;GAO Qun;PAN Yi;JIA Wenhao;LIN Qian(Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing,100700;Beijing University of Chinese Medicine Third Affiliated Hospital)

机构地区：[1]北京中医药大学东直门医院,北京市100700 [2]北京中医药大学第三附属医院

出　　处：《中医杂志》2024年第11期1180-1188,共9页Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金(82074188);北京中医药大学新教师启动基金项目(2021-JYB-XJSJJ-080)。

摘　　要：目的 从代谢组学角度对比分析益气凉血生肌方与阿托伐他汀对大鼠血管损伤修复的影响及可能机制。方法 将24只SD大鼠随机分为假手术组、模型组、益气凉血生肌方组、阿托伐他汀组,每组6只。除假手术组外其余各组大鼠采用球囊拉伤腹主动脉构建血管损伤大鼠模型。各组大鼠术后当天开始灌胃,假手术组、模型组大鼠灌胃去离子水15 ml/(kg·d),益气凉血生肌方组予益气凉血生肌方混悬液6 g/(kg·d)灌胃,阿托伐他汀组予阿托伐他汀混悬液2 mg/(kg·d)灌胃。各组均连续灌胃4周后,HE染色观察腹主动脉损伤段病理形态;ELISA法检测血清一氧化氮(NO)及C反应蛋白(CRP)水平;采用超高效液相色谱-质谱联用(UPLC–MS/MS)技术进行血清广泛靶向代谢组学检测,运用多元统计分析方法筛选两种药物的代谢标志物及代谢途径;比较各组大鼠两种药物血清关键代谢标志物水平。结果 与假手术组相比,模型组大鼠腹主动脉病理显示新生内膜明显增生,检测血清NO水平明显降低、CRP水平明显升高(P<0.01);与模型组相比,益气凉血生肌方组与阿托伐他汀组大鼠动脉内膜增生程度均减轻,血清NO水平升高、CRP水平下降(P<0.05或P<0.01)。血清代谢组学结果显示,益气凉血生肌方组获得49种代谢标志物、6条代谢途径,阿托伐他汀组获得41种代谢标志物、4条代谢途径。两种药物共同调节38种代谢物,甘油磷脂代谢和精氨酸相关代谢是两种药物的共同代谢途径,溶血磷脂酰胆碱(16∶1/0∶0)[LPC (16∶1/0∶0)]、磷脂酰胆碱(15∶0/15∶0)[PC (15∶0/15∶0)]为甘油磷脂代谢途径的关键代谢物,鸟氨酸、亚精胺为精氨酸相关代谢途径的关键代谢物。三羧酸循环、谷胱甘肽代谢是益气凉血生肌方独有的代谢途径。与假手术组相比,模型组LPC (16∶1/0∶0)、鸟氨酸、亚精胺水平均升高,PC (15∶0/15∶0)水平下降(P<0.05或P<0.01)。与模型Objective To compare the effects and differences of Yiqi Liangxue Shengji Formula(益气凉血生肌方)and atorvastatin on the repair of vascular injury in rats from the perspective of metabolomics.Methods Twenty-four male SD rats were randomly divided into sham-surgery,model,traditional Chinese medicine(TCM),and ator-vastatin groups,with 6 rats in each group.The rat model was established by balloon-induced abdominal aorta injury.Gavage was started on the day after surgery in all groups of rats.The sham and model groups were given with deio-nized water,TCM group received Yiqi Liangxue Shengji Formula 6 g/(kg·d),and the atorvastatin group treated with atorvastatin suspension 2 mg/(kg·d)for 4 weeks.HE staining was used to observe the pathological morphology of the injured segment of the abdominal aorta;ELISA detection was used to test serum nitric oxide(NO)and C-reactive protein(CRP)levels;UPLC MS/MS technology was used for widely targeted metabolomics detection in serum,and multivariate statistical analysis was used to screen metabolic markers and pathways of two drugs;finally,compare serum levels of key metabolic markers of the above two medications in rats of each group.Results Compared with the sham-surgery group,the neointima significantly thickened,the level of NO decreased significantly and the level of CRP increased in serum of the model group(P<0.01);compared with the model group,the degree of arterial intimal hyperplasia in TCM group and atorvastatin group reduced,with an increase in NO levels and a decrease in CRP levels(P<0.05 or P<0.01).The results of serum metabolomics showed that TCM group obtained 49 metabolic markers and 6 metabolic pathways,while atorvastatin group obtained 41 metabolic markers and 4 metabolic pathways.The two medications jointly regulated 38 metabolites.Glycerophospholipid metabolism and arginine-related metabolism were common metabolic pathways for both medications.Lysophosphatidylcholine(16∶1/0∶0)[LPC(16∶1/0∶0)],phosphatidylcholine(15∶0/15∶0)[PC(15∶0/15∶0)]we

关 键 词：经皮冠状动脉介入术 血管损伤 益气凉血生肌方 阿托伐他汀 不良心血管事件 代谢组学 

分 类 号：R285.5[医药卫生—中药学] R965[医药卫生—中医学]