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脑脊液丙酮酸脱氢酶激酶4水平升高是蛛网膜下腔出血后临床预后的预测生物标志物。

Elevated Level of Cerebrospinal Fluid Pyruvate Dehydrogenase Kinase 4 Is a Predictive Biomarker of Clinical Outcome after Subarachnoid Hemorrhage.

作者信息

Gao Xuan, Zhang Huasheng, Peng Zheng, Zhuang Zong, Li Wei

机构信息

Department of Neurosurgery, Tianjin Huanhu Hospital, Tianjin 300333, China.

Department of Neurosurgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China.

出版信息

Brain Sci. 2022 Nov 6;12(11):1507. doi: 10.3390/brainsci12111507.

Abstract

Subarachnoid hemorrhage (SAH) is a central nervous system disease with high mortality and morbidity. Some independent factors valuable for prognosis prediction in patients with SAH are still lacking. In our earlier study, we found that PDK4 exerts a protective effect after SAH, primarily by reducing oxidative stress and neuronal death via the ROS/ASK1/p38 signaling pathway. Therefore, we investigated the changes in the level of pyruvate dehydrogenase kinase 4 (PDK4) in patients after subarachnoid hemorrhage (SAH) and analyzed the value of the cerebrospinal fluid (CSF) PDK4 level in predicting the prognoses of patients with SAH after interventional embolization surgery. Some knee arthritis subjects who needed surgery were recruited as a control group. The results showed that PDK4 expression was elevated in the CSF of SAH patients compared with that of controls. PDK4 levels in CSF (OR = 4.525; 95% CI: 1.135-18.038; = 0.032), time to surgery (OR = 0.795; 95% CI: 0.646-0.977; = 0.029), and initial GCS scores (OR = 2.758; 95% CI: 0.177-43.106; = 0.469) were independent prognostic risk factors for SAH patients after surgery. The receiver operating characteristic (ROC) curve showed PDK4 levels in CSF had a higher predictive value. Thus, PDK4 in CSF could be an independent prognostic risk factor for SAH patients after surgery. PDK4 has the potential to serve as a new therapeutic target and biomarker for use in the diagnosis of SAH severity and the prediction of recovery.

摘要

蛛网膜下腔出血(SAH)是一种死亡率和发病率都很高的中枢神经系统疾病。目前仍缺乏一些对SAH患者预后预测有价值的独立因素。在我们早期的研究中,我们发现PDK4在SAH后发挥保护作用,主要是通过ROS/ASK1/p38信号通路减少氧化应激和神经元死亡。因此,我们研究了蛛网膜下腔出血(SAH)患者术后丙酮酸脱氢酶激酶4(PDK4)水平的变化,并分析了脑脊液(CSF)中PDK4水平在预测SAH患者介入栓塞术后预后中的价值。招募了一些需要手术的膝关节炎患者作为对照组。结果显示,与对照组相比,SAH患者脑脊液中PDK4表达升高。脑脊液中PDK4水平(OR = 4.525;95%CI:1.135 - 18.038;P = 0.032)、手术时间(OR = 0.795;95%CI:0.646 - 0.977;P = 0.029)和初始格拉斯哥昏迷量表(GCS)评分(OR = 2.758;95%CI:0.177 - 43.106;P = 0.469)是SAH患者术后独立的预后危险因素。受试者工作特征(ROC)曲线显示脑脊液中PDK4水平具有较高的预测价值。因此,脑脊液中的PDK4可能是SAH患者术后独立的预后危险因素。PDK4有潜力作为一种新的治疗靶点和生物标志物,用于SAH严重程度的诊断和恢复情况的预测。

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