血浆代谢物丙酮酸对急性Stanford B型主动脉夹层的预测诊断价值

The Predictive Diagnostic Value of Plasma Metabolite Pyruvate for Acute Stanford B Aortic Dissection

摘要: 目的：观察急性Stanford B型主动脉夹层(Aortic Dissection, AD)患者血浆代谢物丙酮酸水平变化，探讨其预测诊断价值。方法：选取2023年1月至2024年1在新疆医科大学第一附属医院诊治的急性Stanford B型AD患者及健康对照组，进行非靶向代谢物组学检测及扩大人群ELISA实验验证。结果：筛选出胍基丁胺、N-乙酰苯丙氨酸、D-甘油酸等代谢物在AD组中含量明显高于HC组，分布差异有统计学意义(P < 0.001)。而L-组氨酸、L-瓜氨酸、1-硬脂酰-2-花生酰-SN-甘油、L-乳酸、sn-甘油-3-磷酸胆碱、L-脯氨酸、2-磷酸-D-甘油酸、丙酮酸、L-鸟氨酸、烟酸等代谢物在AD组中含量低于HC组，分布差异有统计学意义(P < 0.001)，其中丙酮酸与主动脉夹层相关性最强(r = −0.835)。扩大人群(AD = 82, HC = 82)用丙酮酸酶联免疫吸附测定(Enzyme-Linked Immunosorbent Assay, ELISE)试剂盒进行验证，得到AD vs HC组中丙酮酸在AD组中的含量低于HC组，差异有统计学意义(AD: 1.527 ± 0.215; HC: 2.116 ± 0.249, AD vs HC, P < 0.001)。进一步行丙酮酸与AD患者血生化指标间的相关性分析得出丙酮酸与尿酸、甘油三脂、总胆固醇、高密、低密、总胆红素及CK-MB等均正相关，皮尔逊相关系数r分别是0.025、0.015、0.210、0.264、0.293、0.170，而与尿素、肌酐、血糖、总胆红素、直胆、非结合胆红素胆、CK、D二聚体、C反应蛋白、白介素-6及降钙素原等均负相关，皮尔逊相关系数r为−0.05、−0.215、−0.037、−0.265、−0.084、−0.098、−0.168、−0.392、−0.626、−0.457、−0.647。最终丙酮酸预测区分Stanford B型AD和HC，AUC值为0.959，95% CI：0.927~0.990，P < 0.001，约登指数为0.878，灵敏度为0.927，特异度为0.951。结论：急性Stanford B型AD中丙酮酸水平较低，预测诊断急性Stanford B型主动脉夹层的效能良好，可作为潜在的新型生物标志物，为临床上探寻快捷、灵敏的预测诊断方法提供一定的理论基础。

Abstract: Objective: Observing the changes in plasma metabolite pyruvate levels in patients with acute Stanford B aortic dissection (AD) and exploring its predictive diagnostic value. Method: We identified 28 patients with acute Stanford B AD treated at the First Affiliated Hospital of Xinjiang Medical University from January 2022 to July 2023, and matched them with 28 healthy control subjects. Conduct non targeted metabolomics testing and expand population ELISA experiments for validation. Results: The metabolites of Agmatine, N-Acetyl-L-phenylalanine, and D-glycerate Acid were significantly higher in the AD group than in the HC group, and the distribution difference was statistically significant (P < 0.001).The levels of metabolites such as N-2-Phospho-D-glyceric acid, L-Histidine, L-Citrulline, 1-Stearoyl-2-arachidonoyl-SN-glycerol, L-Lactic Acid, Pyruvic Acid, Sn-Glycero-3-Phosphocholine, L-Ornithine, L-Proline and Nicotinic Acid in the AD group were lower than those in the HC group, and the distribution difference was statistically significant (P < 0.001). Among them, pyruvate had the strongest correlation with aortic dissection (r = −0.835). Expanded population (AD = 82, HC = 82) was validated using the Enzyme Linked Immunosorbent Assay (ELISE) kit, and it was found that the content of pyruvate in the AD vs HC group was lower than that in the HC group, with statistical significance (AD: 1.527 ± 0.215; HC: 2.116 ± 0.249, AD vs HC, P < 0.001). Further correlation analysis between pyruvate and blood biochemical indicators in AD patients revealed that pyruvate was positively correlated with uric acid, triglycerides, total cholesterol, high-density, low-density, total bilirubin, and CK-MB, with Pearson correlation coefficients of 0.025, 0.015, 0.210, 0.264, 0.293, and 0.170, respectively. However, it was negatively correlated with urea, creatinine, blood glucose, total bilirubin, straight bile, unconjugated bilirubin bile, CK, D-dimer, C-reactive protein, interleukin-6, and procalcitonin, with Pearson correlation coefficients of −0.05, −0.215, −0.037, −0.265, −0.084. −0.098, −0.168, −0.392, −0.626, −0.457, −0.647. The final prediction of pyruvate distinguishes Stanford B AD and HC, with an AUC value of 0.959, 95% CI: 0.927~0.990, P < 0.001, Youden index of 0.878, sensitivity of 0.927, and specificity of 0.951. Conclusions: The levels of pyruvate in acute Stanford B AD are low, indicating good predictive diagnostic efficacy for acute Stanford B AD. It can serve as a potential new biomarker and provide a theoretical basis for exploring fast and sensitive predictive diagnostic methods in clinical practice.