Laboratory Animal Center, Chinese PLA General Hospital, Beijing, People's Republic of China.
Animal Model Exp Med. 2024 Aug;7(4):419-432. doi: 10.1002/ame2.12462. Epub 2024 Jun 25.
To explore potential biomarkers for early diagnosis of atherosclerosis (AS) and provide basic data for further research on AS, the characteristics of serum metabolomics during the progression of AS in mini-pigs were observed dynamically.
An AS model in Bama miniature pigs was established by a high-cholesterol and high-fat diet. Fasting serum samples were collected monthly for metabolomics and serum lipid detection. At the end of the treatment period, pathological analysis of the abdominal aorta and coronary artery was performed to evaluate the lesions of AS, thereby distinguishing the susceptibility of mini-pigs to AS. The metabolomics was detected using a high-resolution untargeted metabolomic approach. Statistical analysis was used to identify metabolites associated with AS susceptibility.
Based on pathological analysis, mini-pigs were divided into two groups: a susceptible group (n = 3) and a non-susceptible group (n = 6). A total of 1318 metabolites were identified, with significant shifting of metabolic profiles over time in both groups. Dynamic monitoring analysis highlighted 57 metabolites that exhibited an obvious trend of differential changes between two groups with the advance of time. The KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analysis indicated significant disorders in cholesterol metabolism, primary bile acid metabolism, histidine metabolism, as well as taurine and hypotaurine metabolism.
During the progression of AS in mini-pigs induced by high-cholesterol/high-fat diet, the alterations in serum metabolic profile exhibited a time-dependent pattern, accompanied by notable disturbances in lipid metabolism, cholesterol metabolism, and amino acid metabolism. These metabolites may become potential biomarkers for early diagnosis of AS.
为了探索动脉粥样硬化(AS)早期诊断的潜在生物标志物,为 AS 的进一步研究提供基础数据,动态观察小型猪 AS 进展过程中血清代谢组学的特征。
采用高胆固醇、高脂肪饮食建立巴马小型猪 AS 模型。每月采集空腹血清样本进行代谢组学和血清脂质检测。治疗期末,对腹主动脉和冠状动脉进行病理分析,评价 AS 病变,从而区分小型猪对 AS 的易感性。采用高分辨非靶向代谢组学方法进行代谢组学检测。采用统计学分析方法鉴定与 AS 易感性相关的代谢物。
根据病理分析,将小型猪分为易感组(n=3)和非易感组(n=6)。共鉴定出 1318 种代谢物,两组代谢谱随时间均有明显变化。动态监测分析显示,57 种代谢物随时间的差异变化呈明显趋势。KEGG(京都基因与基因组百科全书)通路富集分析表明,胆固醇代谢、初级胆汁酸代谢、组氨酸代谢以及牛磺酸和次牛磺酸代谢显著紊乱。
在高胆固醇/高脂肪饮食诱导的小型猪 AS 进展过程中,血清代谢谱的改变呈现时间依赖性模式,伴随着脂质代谢、胆固醇代谢和氨基酸代谢的显著紊乱。这些代谢物可能成为 AS 早期诊断的潜在生物标志物。