维持性血液透析患者血清Notch同源基因1、维生素K2、成纤维细胞生长因子受体1表达与其发生血管钙化的关系

杨 洁 唐 婷 刘玲玲

中国血液净化 ›› 2026, Vol. 25 ›› Issue (10) : 815-819.

中国血液净化 ›› 2026, Vol. 25 ›› Issue (10) : 815-819. DOI: 10.3969/j.issn.1671-4091.2026.10.004
临床研究

维持性血液透析患者血清Notch同源基因1、维生素K2、成纤维细胞生长因子受体1表达与其发生血管钙化的关系

  • 杨 洁    唐 婷    刘玲玲
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The relationship between serum Notch1, VK2, and FGFR1 expression and vascular calcification in patients undergoing maintenance hemodialysis

  • YANG Jie, TANG Ting, LIU Ling-ling
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摘要

目的 探讨维持性血液透析(maintenance hemodialysis,MHD)患者血清中Notch同源基因1(Notch homolog 1,Notch1)、维生素K2(vitamin K2,VK2)、成纤维细胞生长因子受体1(fibroblast growth factor receptor 1,FGFR1)的表达水平,并分析其与血管钙化发生的关系。 方法 本研究为横断面研究,选取2022年1月—2023年6月河北中石油中心医院收治的MHD患者作为研究对象,根据腹部侧位X线平片将其分为钙化组和无钙化组。采用酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)检测血清Notch1、FGFR1水平,采用高效液相色谱-串联质谱法(high performance liquid chromatography-tandem mass spectrometry,HPLC-MS/MS)检测VK2水平。收集2组患者临床资料,采用多因素Logistic回归分析血管钙化的独立危险因素,并采用受试者工作特征(receiver operating characteristic,ROC)曲线分析Notch1、FGFR1、VK2的预测价值。 结果 本研究共纳入120例患者,其中钙化组78例,无钙化组42例。钙化组患者血清Notch1[(95.67±1.16)ng/L比(91.21±1.20)ng/L,t=81.189,P<0.001]、FGFR1[(12.62±0.28)μg/L比(11.09±0.38)μg/L,t=2.600,P=0.011]水平均高于无钙化组,血清VK2水平[(1.31±0.03)ng/L比(1.48±0.04)ng/L,t=40.391,P<0.001]低于无钙化组。多因素Logistic回归分析表明:长透析龄(OR=1.132,95% CI:1.022~1.253,P=0.017)、高血磷(OR=3.228,95% CI:1.290~8.079,P=0.012)、高全段甲状旁腺激素(intact parathyroid hormone,iPTH)(OR=1.030,95% CI:1.012~1.056,P=0.003)、高Notch1(OR=1.147,95% CI:1.002~1.313,P=0.047)、低VK2(OR=0.503,95% CI:0.339~0.746,P=0.001)、高超敏C反应蛋白(high-sensitivity C-reactive protein,hs-CRP)(OR=5.447,95% CI:1.768~16.778,P=0.003)是MHD患者血管钙化的独立危险因素;ROC分析显示Notch1、VK2、FGFR1单独检测的AUC分别为0.639、0.700、0.656,三者联合检测的AUC提升至0.785;Notch1、VK2、FGFR1单独检测的灵敏度分别为33.33%、80.95%、78.57%,特异度分别为100.00%、59.52%、47.62%;联合检测的灵敏度为76.19%,特异度为73.81%。 结论 MHD患者血清Notch1、FGFR1表达上调,VK2表达下调,其中Notch1和VK2为血管钙化的独立影响因素,联合检测对血管钙化具有更高的预测价值,可为临床早期筛查与干预提供依据。

Abstract

Objective  To investigate the serum expression levels of Notch homolog 1 (Notch1), vitamin K2 (VK2), and fibroblast growth factor receptor 1 (FGFR1) in patients undergoing maintenance hemodialysis (MHD), and to analyze their relationship with the development of vascular calcification.  Methods This cross-sectional study enrolled MHD patients treated at Hebei PetroChina Central Hospital from January 2022 to June 2023. Patients were divided into a calcification group and a non-calcification group based on abdominal lateral X-ray plain films. Serum levels of Notch1 and FGFR1 were measured using enzyme-linked immunosorbent assay (ELISA), and serum VK2 levels were determined by high-performance liquid chromatography–tandem mass spectrometry (HPLC-MS/MS). Clinical data of both groups were collected. Multivariate logistic regression analysis was used to identify independent risk factors for vascular calcification, and receiver operating characteristic (ROC) curves were employed to evaluate the predictive value of Notch1, FGFR1, and VK2.  Results  A total of 120 patients were included in this study, comprising 78 patients in the calcification group and 42 in the non-calcification group. Serum levels of Notch1 [(95.67±1.16) ng/L vs. (91.21±1.20) ng/L, t=81.189, P<0.001] and FGFR1 [(12.62±0.28) μg/L vs. (11.09±0.38) μg/L, t=2.600, P=0.011] were significantly higher in the calcification group than in the non-calcification group, while serum VK2 levels were significantly lower [(1.31±0.03)ng/L vs. (1.48±0.04) ng/L, t=40.391, P<0.001]. Multivariate logistic regression analysis identified prolonged dialysis vintage (OR=1.132, 95% CI: 1.022~1.253, P=0.017), elevated serum phosphorus (OR=3.228, 95% CI: 1.290~8.079, P=0.012), elevated intact parathyroid hormone (iPTH) (OR=1.030, 95% CI: 1.012~1.056, P=0.003), elevated Notch1 (OR=1.147, 95% CI: 1.002~1.313, P=0.047), low VK2 (OR=0.503, 95% CI: 0.339~0.746, P=0.001), and elevated high-sensitivity C-reactive protein (hs-CRP) (OR=5.447, 95% CI: 1.768~16.778, P=0.003) as independent risk factors for vascular calcification in MHD patients. ROC analysis demonstrated that the area under the curve (AUC) values for Notch1, VK2, and FGFR1 alone were 0.639, 0.700, and 0.656, respectively, whereas the combined detection of the three markers yielded an improved AUC of 0.785. The sensitivities of Notch1, VK2, and FGFR1 alone were 33.33%, 80.95%, and 78.57%, with specificities of 100.00%, 59.52%, and 47.62%, respectively; the combined detection achieved a sensitivity of 76.19% and a specificity of 73.81%. Conclusion  Serum Notch1 and FGFR1 expressions are up-regulated, while VK2 expression is down-regulated in MHD patients. Notch1 and VK2 are independent influencing factors for VC. The combined detection of these markers demonstrates high predictive value for VC, potentially providing a basis for early clinical screening and intervention.

关键词

维持性血液透析 / 血管钙化 / Notch同源基因1 / 维生素K2 / 成纤维细胞生长因子受体1

Key words

Maintenance hemodialysis / Vascular calcification / Notch1 / Vitamin K2 / F ibroblast growth factor receptor 1

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杨 洁 唐 婷 刘玲玲. 维持性血液透析患者血清Notch同源基因1、维生素K2、成纤维细胞生长因子受体1表达与其发生血管钙化的关系[J]. 中国血液净化. 2026, 25(10): 815-819 https://doi.org/10.3969/j.issn.1671-4091.2026.10.004
YANG Jie, TANG Ting, LIU Ling-ling. The relationship between serum Notch1, VK2, and FGFR1 expression and vascular calcification in patients undergoing maintenance hemodialysis[J]. Chinese Journal of Blood Purification. 2026, 25(10): 815-819 https://doi.org/10.3969/j.issn.1671-4091.2026.10.004
中图分类号: R459.5   

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廊坊市科技计划项目(2024013096)

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