血浆代谢物丙酮酸影响血管平滑肌细胞凋亡的研究

目的:旨在探索血浆代谢物丙酮酸对血管平滑肌细胞的凋亡作用。方法:选取人血管平滑肌细胞(vascular smooth muscle cell, VSMC),用血管紧张素II (Angiotensin II, Ang II)干预刺激细胞建立VSMC损伤模型,用不同浓度的特异性代谢物丙酮酸干预损伤细胞,再通过CCK8、TUNEL及流式等实验检测细胞凋亡情况。结果:VSMC细胞活力以Ang II浓度梯度依赖性降低。不同浓度的丙酮酸对VSMC细胞活力的影响不同,并在一定的浓度范围内丙酮酸对细胞活力的影响没有统计学差异。Ang II诱导的VSMC受损细胞模型中用丙酮酸干预之后呈现细胞活力恢复趋势。当丙酮酸(2 mmol/L)干预Ang II诱导的VSMC受损细胞模型时可以在一定程度上恢复细胞凋亡。结论:丙酮酸恢复Ang II干预损伤的血管平滑肌细胞活力。丙酮酸抑制Ang II干预的血管平滑肌细胞进一步凋亡。

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

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 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.

血浆代谢物棕榈酸对急性Stanford B型主动脉夹层的诊断价值

目的观察急性Stanford B型主动脉夹层(TBAD)患者血浆代谢物棕榈酸水平变化,探讨其对急性TBAD的诊断价值。方法2022年1月—2023年7月新疆医科大学第一附属医院诊治急性TBAD患者30例为TBAD组,健康体检者30例为对照组,检测2组血浆代谢物棕榈酸水平,比较2组空腹血糖、尿素等临床资料,采用Pearson相关法分析急性TBAD患者血浆棕榈酸水平与降主动脉内径、降钙素原等指标的相关性;绘制ROC曲线,评估血浆棕榈酸、D-二聚体诊断急性TBAD的效能。结果TBAD组空腹血糖[(7.08±2.50)mmol/L]、尿素[(6.36±2.90)mmol/L]、总胆红素[(21.29±10.33)μmol/L]、D-二聚体[1616.50(805.50,4828.00)μg/L]、C反应蛋白[25.90(7.10,58.53)mg/L]、白细胞介素-6[36.17(20.18,82.88)ng/L]、降钙素原[0.05(0.03,0.13)μg/L]、棕榈酸[(4.35±1.08)g/mL]水平及降主动脉内径[(36.53±4.10)mm]均大于对照组[(6.03±0.96)mmol/L、(5.02±1.08)mmol/L、(8.62±4.96)μmol/L、122.50(62.00,200.00)μg/L、5.60(2.55,7.90)mg/L、3.20(2.45,4.20)ng/L、0.03(0.02,0.04)μg/L、(2.56±0.67)g/mL、(25.83±3.31)mm](t=2.163、2.376、6.056,Z=-6.247、-4.488、-6.654、-2.774,t=7.680、11.119;P均<0.05),直接胆红素[(0.40±0.08)μmol/L]水平及升主动脉内径[(20.63±2.01)mm]均小于对照组[(3.02±1.85)μmol/L、(28.87±5.94)mm](t=-7.712,P=0.001;t=-7.197,P<0.001)。急性TBAD患者血浆棕榈酸水平与降主动脉内径、降钙素原、白细胞介素-6、C反应蛋白、D-二聚体、空腹血糖均呈正相关(r=0.563、0.330、0.495、0.188、0.287、0.349,P均<0.05),与升主动脉内径、直接胆红素均呈负相关(r=-0.544,P<0.001;r=-0.552,P<0.001)。血浆棕榈酸、D-二聚体分别以3.685 g/mL、247.00μg/L为最佳截断值,二者单独及联合诊断急性TBAD的AUC分别为0.932(95%CI:0.872~0.992,P<0.001)、0.969(95%CI:0.926~0.999,P<0.001)、0.993(95%CI:0.980~0.999,P<0.001),灵敏度分别为76.7%、93.3%、96.7%,特异度分别为96.7%、93.3%、96.7%。结论急性TBAD患者血浆棕榈酸水平增高,血浆棕榈酸联合D-二聚体对急性TBAD有较高诊断价值。