不同血瘀程度对冠心病患者认知功能及血浆差异代谢物的影响  

Effect of Different Degrees of Blood Stasis on Cognitive Function and Plasma Differential Metabolites in Patients with Coronary Heart Disease

作　　者：徐仕晗 刘艳飞[1] 刘凤岚 王青 徐凤芹[1] 刘玥[1] XU Shihan;LIU Yanfei;LIU Fenglan;WANG Qing;XU Fengqin;LIU Yue(National Clinical Research Center for Chinese Medicine Cardiology,Key Research Laboratory of Combining Diseases and Evidence to Prevent Vascular Aging,National Administration of Traditional Chinese Medicine,Xiyuan Hospital,China Academy of Chinese Medical Sciences,Beijing 100091,China;Graduate School,Guangdong Pharmaceutical University,Guangzhou 510006,China)

机构地区：[1]中国中医科学院西苑医院,国家中医心血管病临床医学研究中心,国家中医药管理局病证结合防治血管衰老重点研究室,北京100091 [2]广东药科大学研究生院,广州510006

出　　处：《中国实验方剂学杂志》2025年第5期167-176,共10页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：中国中医科学院科技创新工程重大攻关项目(CI2021A01406);国家中医药管理局中医药传承与创新“百千万”人才工程岐黄学者项目(02045006)。

摘　　要：目的:通过横断面研究探索冠心病(CAD)血瘀证积分与轻度认知障碍(MCI)的相关性,以及冠心病合并轻度认知障碍(CADMCI)血瘀证的血浆代谢谱改变,并进一步探索不同血瘀程度对CADMCI患者血浆代谢物谱的影响。方法:依据CAD及CAD血瘀证诊断标准,连续纳入来源于2022年10月至2023年10月于中国中医科学院西苑医院住院患者,根据蒙特利尔认知评估(MoCA)量表评分将入组患者分为CADMCI血瘀证组与CAD血瘀证组,通过多因素Logistic回归模型分析血瘀证积分与MCI之间的关联,绘制受试者工作特征(ROC)曲线,计算曲线下面积(AUC)评估模型灵敏性和特异性。依据血瘀证积分分别将CADMCI血瘀证组及CAD血瘀证组中前30位患者分为血瘀轻证及血瘀重证,采用超高效液相色谱-四极杆-飞行时间质谱法(UPLC-Q-TOF-MS/MS)对各组患者进行血浆代谢物检测,按照变量重要性投影(VIP)值≥1,差异倍数(FC)<0.67或>1.5,P<0.05筛选差异代谢物,并进一步通过ROC曲线分析评估所筛选的差异代谢物对各分组样本的区分效能。结果:本研究共纳入266例CAD患者。多因素Logistic回归分析表明,CAD血瘀证积分与MCI存在显著的相关性[比值比(OR)=1.619,95%置信区间(CI)1.223~2.142,P<0.001,ROC曲线AUC为0.615(95%CI 0.547~0.683,P=0.001)],表明CAD血瘀证积分对MCI具有一定的预测价值。血浆非靶向代谢组学分析表明,CAD血瘀证与CADMCI血瘀证组间主要差异代谢物为脂质类代谢物,其中磷脂酰胆碱[20∶4(5Z,8Z,11Z,14Z)/P-18∶1(11Z)]具有最佳的区分效能(ROC曲线AUC=0.867,95%CI 0.754~0.942);进一步对血瘀轻证与血瘀重证差异代谢物分析表明,血瘀轻证与血瘀重证间同样以脂质类差异代谢物为主,其中1α,25-二羟基-2β(-2-羟基乙氧基)维生素D3具有区分CAD血瘀轻证与重证的最佳效能(AUC=0.813,95%CI 0.649~0.951),磷脂酰胆碱34∶2具有区分CADMCI血瘀轻证和重证的最佳效能(AUC=0.819,95%CI 0.640~0.941)。�Objective:To explore the correlation between the blood stasis score of coronary heart disease(CAD)and mild cognitive impairmen(t MCI),as well as the changes in plasma metabolic profile of blood stasis in patients with CAD combined with MCI(CADMCI)through a cross-sectional study,and further explore the impact of different degrees of blood stasis on the plasma metabolite profile of CADMCI patients.Methods:According to the diagnostic criteria of CAD and CAD blood stasis,patients hospitalized in Xiyuan Hospital of China Academy of Chinese Medical Sciences from October 2022 to October 2023 were continuously included.According to the Montreal Cognitive Assessment(MoCA)scale score,the enrolled patients were divided into CADMCI blood stasis group and CAD blood stasis group.The association between blood stasis score and MCI was analyzed by multivariate Logistic regression model.The receiver operating characteristic(ROC)curve was drawn,and the area under the curve(AUC)was calculated to evaluate the sensitivity and specificity of the model.According to the blood stasis score,the first 30 patients in the CADMCI blood stasis group and CAD blood stasis group were divided into mild blood stasis and severe blood stasis.Ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS)was used to detect plasma metabolites in each group of patients.The differential metabolites were screened according to variable importance in the projection(VIP)value≥1,fold change(FC)<0.67 or>1.5,and P<0.05.ROC curve analysis was further used to evaluate the discriminatory efficiency of the screened differential metabolites for each group of samples.Results:A total of 266 CAD patients were included in this study.Multivariate Logistic regression analysis showed that the CAD blood stasis score was significantly correlated with MCI[odds ratio(OR)=1.619,95%confidence interval(CI)1.223-2.142,P<0.001,ROC curve AUC was 0.615(95%CI 0.547-0.683,P=0.001)],indicating that the CAD blood stasis score has a certain predictiv

关 键 词：冠心病 轻度认知障碍 血瘀证积分 代谢组学 相关性 磷脂酰胆碱 LOGISTIC回归模型 

分 类 号：R256[医药卫生—中医内科学] R541[医药卫生—中医学] R241