尿激酶型纤溶酶原激活物受体（uPAR）和纤连蛋白（cFn）作为急性缺血性卒中患者对重组组织型纤溶酶原激活剂（rtPA）反应低下的候选蛋白质生物标志物。
uPAR and cFn as candidate protein biomarkers for identifying low response to rtPA in acute ischemic stroke.
作者信息
Wang Yilin, Huang Yuyou, Li Fangfang, Han Ziping, Yang Zhenhong, Zhong Liyuan, Li Lingzhi, Zhao Haiping, Fan Junfen, Zheng Yangmin, Borlongan Cesario, Luo Yumin
机构信息
Institute of Cerebrovascular Disease Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, 45 Changchun Street, Beijing, 100053, China.
Department of Neurological Disease Center and Cerebrovascular Diseases Inpatient Ward 1, Beijing Anzhen Hospital Capital Medical University, Beijing, China.
出版信息
Eur J Med Res. 2025 Jul 24;30(1):662. doi: 10.1186/s40001-025-02772-4.
BACKGROUND
Recombinant tissue plasminogen activator (rtPA) remains the main therapeutic for acute ischemic stroke (AIS). In clinical practice, the patients with AIS presenting low response to rtPA is commonly observed. Cognizant that the endothelial cell function is impaired in AIS, this study explored the endothelial cell-associated proteins as biomarkers that may identify low response to rtPA in AIS.
METHODS
Spearman's correlation test was performed to assess the relationship between urokinase-type plasminogen activator receptor (uPAR)/cellular fibronectin (cFn) and AIS outcomes. We defined "low response to rtPA" as the patients did not present a lower National Institute of Health Stroke Scale (NIHSS) than at admission and still suffered from poor outcome (modified Rankin Scale > 2) with rtPA use. Logistic regression analysis was used to assess the contribution of uPAR/cFn in identifying low response to rtPA in AIS. The relationship between uPAR/cFn and rtPA was further probed in Sprague-Dawley rats with experimental stroke induced by middle cerebral artery occlusion.
RESULTS
Both uPAR (P < 0.001) and cFn (P = 0.001) positively correlated with AIS favorable outcomes. uPAR (AUC = 68.2%, P = 0.007) and cFn (AUC = 71.3%, P = 0.002) can identify low response to rtPA. Additionally, uPAR (P = 0.015) and cFn (P = 0.004) were independent variables that predicted low response to rtPA. At 24 h and 72 h ischemic/reperfusion, rtPA tended to decrease cFn and uPAR plasma levels.
CONCLUSIONS
Our study suggests that uPAR and cFn may serve as the candidate markers for identifying low response to rtPA in AIS. Patients with a low plasma level of cFn or uPAR may present low response to rtPA and still suffer from a poor outcome with rtPA.
背景
重组组织型纤溶酶原激活剂（rtPA）仍然是急性缺血性卒中（AIS）的主要治疗药物。在临床实践中，经常观察到AIS患者对rtPA反应不佳。认识到AIS患者的内皮细胞功能受损，本研究探索了与内皮细胞相关的蛋白质作为生物标志物，以识别AIS患者对rtPA的低反应。
方法
采用Spearman相关性检验评估尿激酶型纤溶酶原激活剂受体（uPAR）/细胞纤连蛋白（cFn）与AIS预后之间的关系。我们将“对rtPA低反应”定义为使用rtPA后患者美国国立卫生研究院卒中量表（NIHSS）评分未低于入院时且预后仍较差（改良Rankin量表>2）。采用逻辑回归分析评估uPAR/cFn在识别AIS患者对rtPA低反应中的作用。在大脑中动脉闭塞诱导的实验性卒中的Sprague-Dawley大鼠中进一步探究uPAR/cFn与rtPA之间的关系。
结果
uPAR（P<0.001）和cFn（P=0.001）均与AIS良好预后呈正相关。uPAR（AUC=68.2%，P=0.007）和cFn（AUC=71.3%，P=0.002）可识别对rtPA的低反应。此外，uPAR（P=0.015）和cFn（P=0.004）是预测对rtPA低反应的独立变量。在缺血/再灌注24小时和72小时时，rtPA倾向于降低cFn和uPAR血浆水平。
结论
我们的研究表明，uPAR和cFn可能作为识别AIS患者对rtPA低反应的候选标志物。血浆cFn或uPAR水平低的患者可能对rtPA反应低，使用rtPA后仍预后较差。
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