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基于脂质组学的载脂蛋白E基因敲除小鼠动脉粥样硬化不同进展的预测模型

Prediction model for different progressions of Atherosclerosis in ApoE mice based on lipidomics.

作者信息

Wang Huanhuan, Zhang Lishi, Zhang Xiaoran, Song Jiannan, Guo Qin, Zhang Xude, Bai Dong

机构信息

Institute of Basic Theory of Traditional Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China; School of Basic Medicine, Shaanxi University of Traditional Chinese Medicine, Xianyang, Shaanxi, 712046, China.

Institute of Basic Theory of Traditional Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China.

出版信息

J Pharm Biomed Anal. 2022 May 30;214:114734. doi: 10.1016/j.jpba.2022.114734. Epub 2022 Apr 2.

Abstract

Atherosclerosis (AS) is a progressive disease with a complex pathogenesis which is characterized by dyslipidemia and changes in the vascular wall composition. According to the degree of lesions, atherosclerosis can be divided into four stages: hyperlipidemia, lipid stria, fiber plaque, and atherosclerotic plaque. The present study aimed to establish a prediction model for the different pathological stages of AS based on lipidomics. ApoE mice and C57BL/6 mice fed a normal diet were divided into seven groups according to the feeding time (8, 12, 16, 20, 24, 28, and 32 weeks). The changes in the lipid composition and serum content were detected using ultra-performance liquid chromatography coupled with quadrupole time-of-flight high-definition mass spectrometry (UPLC-Q-TOF/MS). Through the results of serum total cholesterol, triglyceridelow density lipoprotein at each time and HE staining of the head and arm artery, the seven time points of the model group were corresponding to the four courses of atherosclerosis. In accordance with the lipid data of each course of AS and mathematical modeling, this study established a multi-index prediction model of the different processes of AS. Notably, while establishing the model, several indicators were combined with one of four dimension reduction methods, such as principal component logistics regression method, cumulative logistics regression method, Partial least squares-discriminant analysis(PLS-DA), and canonical discriminant analysis (CDA). The error rate of the four methods were 28.5%, 16.22%, 18.24%, and 14.86%, respectively. CDA had the lowest error rate and the best prediction accuracy of the AS different courses for the training and verification sets after 5-fold cross-validation of this model. This study showed that lipidomics combined with mathematical methods could establish a non-invasive and accurate model for the prediction of AS.

摘要

动脉粥样硬化(AS)是一种发病机制复杂的进行性疾病,其特征为血脂异常和血管壁成分改变。根据病变程度,动脉粥样硬化可分为四个阶段:高脂血症、脂纹、纤维斑块和动脉粥样硬化斑块。本研究旨在基于脂质组学建立AS不同病理阶段的预测模型。将喂食正常饮食的载脂蛋白E(ApoE)小鼠和C57BL/6小鼠根据喂养时间(8、12、16、20、24、28和32周)分为七组。使用超高效液相色谱联用四极杆飞行时间高清质谱(UPLC-Q-TOF/MS)检测脂质组成和血清含量的变化。通过各时间点血清总胆固醇、甘油三酯、低密度脂蛋白的结果以及头臂动脉的苏木精-伊红(HE)染色,模型组的七个时间点对应动脉粥样硬化的四个病程。根据AS各病程的脂质数据和数学建模,本研究建立了AS不同进程的多指标预测模型。值得注意的是,在建立模型时,将几个指标与四种降维方法之一相结合,如主成分逻辑回归法、累积逻辑回归法、偏最小二乘判别分析(PLS-DA)和典型判别分析(CDA)。这四种方法的错误率分别为28.5%、16.22%、18.24%和14.86%。对该模型进行五折交叉验证后,CDA的错误率最低,对训练集和验证集的AS不同病程具有最佳预测准确性。本研究表明,脂质组学结合数学方法可为AS的预测建立一种非侵入性且准确的模型。

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