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中华脑血管病杂志(电子版) ›› 2025, Vol. 19 ›› Issue (06) : 483 -489. doi: 10.3877/cma.j.issn.1673-9248.2025.06.005

临床研究

小窝蛋白-1对前循环大血管闭塞患者桥接治疗后颅内出血转化的预测价值
孙程贺(), 田润杞, 王储, 李跃龙   
  1. 161000 黑龙江 齐齐哈尔,齐齐哈尔市第一医院神经内科
  • 收稿日期:2025-10-10 出版日期:2025-12-01
  • 通信作者: 孙程贺
  • 基金资助:
    黑龙江省卫生健康委员会科研课题(20240303070251)

Predictive value of caveolin-1 level for hemorrhagic transformation after bridging therapy in patients with anterior circulation large vessel occlusion

Chenghe Sun(), Runqi Tian, Chu Wang, Yuelong Li   

  1. Department of Neurology, the First Hospital of Qiqihar, Qiqihar 161000, China
  • Received:2025-10-10 Published:2025-12-01
  • Corresponding author: Chenghe Sun
引用本文:

孙程贺, 田润杞, 王储, 李跃龙. 小窝蛋白-1对前循环大血管闭塞患者桥接治疗后颅内出血转化的预测价值[J/OL]. 中华脑血管病杂志(电子版), 2025, 19(06): 483-489.

Chenghe Sun, Runqi Tian, Chu Wang, Yuelong Li. Predictive value of caveolin-1 level for hemorrhagic transformation after bridging therapy in patients with anterior circulation large vessel occlusion[J/OL]. Chinese Journal of Cerebrovascular Diseases(Electronic Edition), 2025, 19(06): 483-489.

目的

评估基线血清小窝蛋白-1(Cav-1)水平对前循环大血管闭塞患者桥接治疗后颅内出血转化(HT)的预测价值。

方法

纳入2022年1月至2024年12月齐齐哈尔市第一医院接受桥接治疗的前循环大血管闭塞患者为研究对象,根据HT情况将患者分为出血组26例和非出血组52例。收集2组患者的临床资料,包括一般资料、头部影像学、实验室指标及基线血清Cav-1水平等。分析基线血清Cav-1水平能否作为桥接治疗后HT的独立预测因素。根据患者治疗后3个月的改良Rankin量表(mRS)评分是否≤2分以及死亡情况判断基线血清Cav-1水平对预后的影响。计量资料采用独立样本t检验或Mann-Whitney U检验;采用Logistic回归分析影响颅内HT的独立因素,并绘制受试者操作特征(ROC)曲线。

结果

出血组与未出血组患者的随机血糖水平分别为8.28(6.34,10.99)和6.22(5.46,8.28)mmol/L,基线血清Cav-1水平分别为109.50(103.75,117.25)和117.00(111.50,127.75)ng/L,基线Alberta卒中项目早期CT评分(ASPECTS)分别为8.00(7.00,10.00)和9.00(8.00,10.00)分,基线美国国立卫生研究院卒中量表(NIHSS)评分分别为(15.65±2.62)和(13.92±3.26)分,差异均有统计学意义(Z=-2.459、2.487、-2.600,t=2.352;P=0.014、0.020、0.009、0.021)。多因素分析显示:基线血清Cav-1水平(OR=0.90,95%CI:0.84~0.97,P=0.006)、ASPECTS评分(OR=0.56,95%CI:0.33~0.92,P=0.022)、NIHSS评分(OR=1.34,95%CI:1.06~1.69,P=0.013)、收缩压(OR=1.03,95%CI:1.01~1.06,P=0.018)均是前循环大血管闭塞患者桥接治疗后HT的独立影响因素。ROC曲线分析显示:基线血清Cav-1水平列线图预测模型的曲线下面积最大,为0.71(95%CI:0.60~0.82)。预后良好组与预后不良组患者的基线血清Cav-1水平分别为118.50(111.00,129.00)和113.00(104.00,117.00)ng/L,差异有统计学意义(Z=-2.852,P=0.004)。死亡组与非死亡组患者的基线血清Cav-1水平分别为114.00(106.00,116.50)和116.00(108.00,123.50)ng/L,差异无统计学意义(Z=-1.127,P=0.260)。

结论

出血组患者基线血清Cav-1水平及ASPECTS评分偏低,NIHSS评分及收缩压偏高。低基线血清Cav-1水平可预测桥接治疗后HT,高基线血清Cav-1水平与治疗后3个月良好预后相关,而基线血清Cav-1水平对治疗后3个月病死率无显著影响。

Objective

To evaluate the predictive value of baseline serum caveolin-1 (Cav-1) level for hemorrhagic transformation (HT) after bridging therapy in patients with anterior circulation large vessel occlusion.

Methods

Patients with anterior circulation large vessel occlusion who underwent bridging therapy at the First Hospital of Qiqihar from January 2022 to December 2024 were enrolled. They were divided into the hemorrhagic group (n=26) and non-hemorrhagic group (n=52) according to the presence of HT. Clinical data of the two groups were collected, including general information, cranial imaging findings, laboratory indicators, and baseline serum Cav-1 level. We analyzed whether baseline Cav-1 level could serve as an independent predictor of HT after bridging therapy. Additionally, the impact of baseline serum Cav-1 level on prognosis was evaluated based on whether the modified Rankin scale (mRS) score was ≤2 at 3 months and the mortality status of patients. The differences of measurement data were analyzed using independent sample t-test or Mann-Whitney U test. The Logistic analysis was used to identify the independent factors influencing intracranial HT, and the receiver operator characteristic (ROC) curve was plotted.

Results

The hemorrhagic group had higher random blood glucose [8.28 (6.34, 10.99) mmol/L vs 6.22 (5.46, 8.28) mmol/L, Z=-2.459, P=0.014], lower baseline Cav-1 [109.50 (103.75, 117.25) ng/L vs 117.00 (111.50, 127.75) ng/L, Z=2.487, P=0.020], lower ASPECTS [8.00 (7.00, 10.00) vs 9.00 (8.00, 10.00), Z=-2.600, P=0.009], and higher National Institute of Health stroke scale (NIHSS) scores (15.65±2.62 vs 13.92±3.26, t=2.352, P=0.021). Multivariate analysis showed that baseline serum Cav-1 level (OR=0.90, 95%CI: 0.84-0.97, P=0.006), ASPECTS (OR=0.56, 95%CI: 0.33-0.92, P=0.022), NIHSS score (OR=1.34, 95%CI: 1.06-1.69, P=0.013), and systolic blood pressure (OR=1.03, 95%CI: 1.01-1.06, P=0.018) were all independent influencing factors for HT after bridging therapy in patients with anterior circulation large vessel occlusion. Results of the ROC curve indicated that the area under the curve (AUC) of the nomogram prediction model based on baseline serum Cav-1 level was the largest, at 0.71 (95%CI: 0.60-0.82). Higher baseline Cav-1 was associated with good prognosis [118.50 (111.00, 129.00) ng/L vs 113.00 (104.00, 117.00) ng/L, Z=-2.852, P=0.004] but not with mortality [114.00 (106.00, 116.50) ng/L vs 116.00 (108.00, 123.50) ng/L, Z=-1.127, P=0.260].

Conclusion

In the hemorrhagic group, baseline serum Cav-1 level and ASPECTS score were lower while NIHSS score and systolic blood pressure were higher; a low baseline serum Cav-1 level could predict HT after bridging therapy, while a high baseline serum Cav-1 level is associated with better prognosis at 3 months, without significant impact on mortality.

表1 出血组与非出血组前循环大血管闭塞患者基线特征比较
变量 总体(n=78) 出血组(n=26) 非出血组(n=52) 统计值 P
年龄(岁,
±s
69.14±10.82 70.58±9.71 68.42±11.36 t=0.871 0.387
男[例(%)] 53(67.95) 17(65.38) 36(69.23) χ2=118.000 0.732
既往史[例(%)]
高血压史 51(65.38) 18(69.23) 33(63.46) χ2=0.255 0.614
糖尿病史 23(29.49) 11(42.31) 12(23.08) χ2=3.083 0.079
冠心病史 21(26.92) 7(26.92) 14(26.92) χ2=0.000 1.000
卒中史 22(28.21) 6(23.08) 16(30.77) χ2=0.506 0.477
心房颤动史 20(25.64) 7(26.92) 13(25.00) χ2=0.034 0.855
基线收缩压(mmHg,
±s
146.60±24.68 154.19±24.00 142.81±24.36 t=1.955 0.054
基线舒张压(mmHg,
±s
84.15±14.18 86.73±14.90 82.87±13.77 t=1.137 0.259
从发病到再通的时间[h,MQ1Q3)] 6.45(4.58,8.83) 7.43(4.98,9.77) 6.20(4.35,8.53) Z=-1.140 0.159
从发病至治疗的时间[h,MQ1Q3)] 3.20(2.30,3.83) 3.50(2.60,4.13) 3.20(2.23,3.80) Z=-1.374 0.169
使用替罗非班[例(%)] 47(60.26) 16(61.54) 31(59.62) χ2=0.027 0.870
取栓次数[例(%)] χ2=0.915 0.633
1次 58(74.36) 20(76.92) 38(73.08)
2次 14(17.95) 5(19.23) 9(17.31)
3次 6(7.69) 1(3.85) 5(9.62)
NIHSS评分(分,
±s
14.50±3.15 15.65±2.62 13.92±3.26 t=2.352 0.021
ASPECTS评分[分,MQ1Q3)] 9.00(8.00,10.00) 8.00(7.00,10.00) 9.00(8.00,10.00) Z=-2.600 0.009
闭塞血管[例(%)] χ2=1.020 0.313
颈内动脉 27(34.62) 11(42.31) 16(30.77)
大脑中动脉 51(65.38) 15(57.69) 36(69.23)
卒中分型[例(%)] χ2=1.671 0.434
LAA 37(47.44) 15(57.69) 22(42.31)
CE 29(37.18) 8(30.77) 21(40.38)
UDE 12(15.38) 3(11.54) 9(17.31)
RBG[mmol/L,MQ1Q3)] 6.71(5.50,9.43) 8.28(6.34,10.99) 6.22(5.46,8.28) Z=-2.459 0.014
CRP[mg/L,MQ1Q3)] 7.89(3.48,16.35) 7.73(2.57,19.96) 7.89(3.97,15.36) Z=-0.032 0.975
D-D[mg/L,MQ1Q3)] 1.56(0.60,5.03) 2.35(0.94,5.17) 1.44(0.56,4.88) Z=-1.081 0.280
FIB(g/L,
±s
3.03±1.03 2.81±0.14 3.15±0.16 t=-1.376 0.176
HCY[µmol/L,MQ1Q3)] 14.40(11.88,17.25) 14.35(11.25,17.43) 14.55(11.90,17.13) Z=-0.668 0.504
HDL[mmol/L,MQ1Q3)] 1.10(0.97,1.37) 1.12(0.98,1.26) 1.09(0.91,1.40) Z=-0.111 0.911
LDL[mmol/L,MQ1Q3)] 2.36(1.99,3.05) 2.24(1.92,3.19) 2.44(2.03,3.03) Z=-1.060 0.289
TG[mmol/L,MQ1Q3)] 1.00(0.75,1.58) 0.95(0.72,1.73) 1.07(0.78,1.55) Z=-0.816 0.414
Cav-1[ng/L,MQ1Q3)] 115.50(108.50,122.00) 109.50(103.75,117.25) 117.00(111.50,127.75) Z=2.487 0.020
表2 前循环大血管闭塞患者桥接治疗后颅内出血转化的二元多因素Logistic回归分析
表3 前循环大血管闭塞患者桥接治疗后颅内出血转化预测值的受试者操作特征曲线分析
图1 前循环大血管闭塞患者桥接治疗后颅内出血转化因素的受试者操作特征曲线
1
GBD 2019 Stroke Collaborators. Global, regional, and national burden of stroke and its risk factors, 1990-2019: a systematic analysis for the global burden of disease study 2019 [J]. Lancet Neurol, 2021, 20(10): 795-820.
2
Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association [J]. Stroke, 2019, 50(12): e344-e418.
3
Yang P, Zhang Y, Zhang L, et al. Endovascular thrombectomy with or without intravenous alteplase in acute stroke [J]. N Engl J Med, 2020, 382(21): 1981-1993.
4
Eltzschig HK, Eckle T. Ischemia and reperfusion--from mechanism to translation [J]. Nat Med, 2011, 17(11): 1391-1401.
5
Iadecola C, Anrather J. The immunology of stroke: from mechanisms to translation [J]. Nat Med, 2011, 17(7): 796-808.
6
Castellanos M, Serena J. Applicability of biomarkers in ischemic stroke [J]. Cerebrovasc Dis, 2007, 24 Suppl 1: 7-15.
7
Castellanos M, Sobrino T, Millán M, et al. Serum cellular fibronectin and matrix metalloproteinase-9 as screening biomarkers for the prediction of parenchymal hematoma after thrombolytic therapy in acute ischemic stroke: a multicenter confirmatory study [J]. Stroke, 2007, 38(6): 1855-1859.
8
Jasmin JF, Malhotra S, Singh Dhallu M, et al. Caveolin-1 deficiency increases cerebral ischemic injury [J]. Circ Res, 2007, 100(5): 721-729.
9
Schubert W, Frank PG, Woodman SE, et al. Microvascular hyperpermeability in caveolin-1-/- knock-out mice. Treatment with a specific nitric-oxide synthase inhibitor, L-NAME, restores normal microvascular permeability in Cav-1 null mice [J]. J Biol Chem, 2002, 277(42): 40091-40098.
10
Castellanos M, van Eendenburg C, Gubern C, et al. Low levels of caveolin-1 predict symptomatic bleeding after thrombolytic therapy in patients with acute ischemic stroke [J]. Stroke, 2018, 49(6): 1525-1527.
11
Wang Q, Cao H, E Y, et al. The prognostic value of caveolin-1 levels in ischemic stroke patients after mechanical thrombectomy [J]. Neurol Sci, 2023, 44(6): 2081-2086.
12
中国卒中学会,中国卒中学会神经介入分会, 中华预防医学会卒中预防与控制专业委员会介入学组. 急性缺血性卒中血管内治疗中国指南2018 [J]. 中国卒中杂志, 2018, 13(7): 706-729.
13
Adams HP Jr, Bendixen BH, Kappelle LJ, et al. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in acute stroke treatment [J]. Stroke, 1993, 24(1): 35-41.
14
Nogueira RG, Jadhav AP, Haussen DC, et al. Thrombectomy 6 to 24 hours after stroke with a mismatch between deficit and infarct [J]. N Engl J Med, 2018, 378(1): 11-21.
15
彭涛, 张紫霓, 朱碧峰, 等. 前循环串联病变血管内治疗预后的影响因素分析 [J/OL]. 中华脑血管病杂志(电子版), 2021, 15(5): 319-22.
16
Olthuis SGH, Pirson FAV, Pinckaers FME, et al. Endovascular treatment versus no endovascular treatment after 6-24 h in patients with ischaemic stroke and collateral flow on CT angiography (MR CLEAN-LATE) in the Netherlands: a multicentre, open-label, blinded-endpoint, randomised, controlled, phase 3 trial [J]. Lancet, 2023, 401(10385): 1371-1380.
17
Xu L, Guo R, Xie Y, et al. Caveolae: molecular insights and therapeutic targets for stroke [J]. Expert Opin Ther Targets, 2015, 19(5): 633-650.
18
Sowa G. Caveolae, caveolins, cavins, and endothelial cell function: new insights [J]. Front Physiol, 2012, 2: 120.
19
Parton RG, Del Pozo MA. Caveolae as plasma membrane sensors, protectors and organizers [J]. Nat Rev Mol Cell Biol, 2013, 14(2): 98-112.
20
Zhao YL, Song JN, Zhang M. Role of caveolin-1 in the biology of the blood-brain barrier [J]. Rev Neurosci, 2014, 25(2): 247-254.
21
Chang CF, Chen SF, Lee TS, et al. Caveolin-1 deletion reduces early brain injury after experimental intracerebral hemorrhage [J]. Am J Pathol, 2011, 178(4): 1749-1761.
22
Zhang J, Zhu W, Xiao L, et al. Lower serum caveolin-1 is associated with cerebral microbleeds in patients with acute ischemic stroke [J]. Oxid Med Cell Longev, 2016, 2016: 9026787.
23
Xie Y, Wu M, Li Y, et al. Low caveolin-1 levels and symptomatic intracranial haemorrhage risk in large-vessel occlusive stroke patients after endovascular thrombectomy [J]. Eur J Neurol, 2024, 31(8): e16342.
24
梁俏丽, 陈静娟, 周锋, 等. 胰岛素抵抗与缺血性脑卒中关系的研究进展 [J/OL]. 中华脑血管病杂志(电子版), 2022, 16(2): 120-124.
25
Yuan C, Chen S, Ruan Y, et al. The stress hyperglycemia ratio is associated with hemorrhagic transformation in patients with acute ischemic stroke [J]. Clin Interv Aging, 2021, 16: 431-442.
26
Chen L, Chen N, Lin Y, et al. Glucose to platelet ratio: a potential predictor of hemorrhagic transformation in patients with acute ischemic stroke [J]. Brain Sci, 2022, 12(9): 1170.
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