Pandey Swarnima, Azim Afzal, Sinha Neeraj
Centre of Biomedical Research, SGPGIMS Campus, Raebareli Road, Lucknow 226014, India.
Department of Critical Care Medicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India.
Biophys Chem. 2025 Nov;326:107491. doi: 10.1016/j.bpc.2025.107491. Epub 2025 Jul 9.
Despite the availability of advanced treatment, sepsis and septic shock have the highest mortality in the intensive care unit. Theories suggested that targeting hyper inflammation can aid treatment, but oxidative stress plays a major role in disease pathogenesis. The present study aimed to explore the nuclear magnetic resonance (NMR) - based serum biomarkers of sepsis and septic shock resultant of oxidative stress. The serum metabolic profile of n = 41 septic shock, n = 21 sepsis, and n = 16 disease control patients were collected and analyzed using a 1D H Carr Purcell Meiboom Gill (CPMG) pulse program. NMR spectroscopy-based quantitative assessment of metabolites was performed to compare the activity of lactate dehydrogenase and phenylalanine hydroxylase between sepsis, septic shock, and disease control in sepsis and septic shock by comparing pyruvate/lactate (Pyr/Lac) and phenylalanine/tyrosine (Phe/Tyr) ratios. These ratios were evaluated for their discriminatory potential, statistical and clinical significance. We found out that Pyr/Lac ratio was lowest in septic shock followed by sepsis and disease control, Phe/Tyr ratio was highest in septic shock, followed by sepsis and disease control. Pyr/Lac ratio and Phe/Tyr were negatively and positively correlated with APACHE II. Both the ratios illustrated high discriminatory potential in AUROC evaluation. The results presented in the study demonstrate that lactate dehydrogenase activity is elevated and phenylalanine hydroxylase declines in septic shock. This could be used as an effective tool for diagnosis, prognosis, evaluation of disease activity, and treatment response.
尽管有先进的治疗方法，但脓毒症和脓毒性休克在重症监护病房中的死亡率最高。理论表明，针对过度炎症进行治疗可能会有所帮助，但氧化应激在疾病发病机制中起主要作用。本研究旨在探索基于核磁共振（NMR）的、由氧化应激导致的脓毒症和脓毒性休克的血清生物标志物。收集了n = 41例脓毒性休克患者、n = 21例脓毒症患者和n = 16例疾病对照患者的血清代谢谱，并使用一维H Carr Purcell Meiboom Gill（CPMG）脉冲程序进行分析。通过比较丙酮酸/乳酸（Pyr/Lac）和苯丙氨酸/酪氨酸（Phe/Tyr）比值，对基于核磁共振波谱的代谢物进行定量评估，以比较脓毒症、脓毒性休克以及脓毒症和脓毒性休克中的疾病对照之间乳酸脱氢酶和苯丙氨酸羟化酶的活性。评估了这些比值的鉴别潜力、统计学和临床意义。我们发现，脓毒性休克中的Pyr/Lac比值最低，其次是脓毒症和疾病对照，脓毒性休克中的Phe/Tyr比值最高，其次是脓毒症和疾病对照。Pyr/Lac比值和Phe/Tyr与急性生理学与慢性健康状况评分系统II（APACHE II）呈负相关和正相关。在受试者工作特征曲线（AUROC）评估中，这两个比值均显示出较高的鉴别潜力。该研究结果表明，脓毒性休克中乳酸脱氢酶活性升高，苯丙氨酸羟化酶活性下降。这可作为诊断、预后、疾病活动评估和治疗反应评估的有效工具。
