急性缺血性脑卒中不同分型患者血清LAR、HDAC3、CCL20水平变化及其与神经功能早期恶化的关系-东南大学学报医学版

急性缺血性脑卒中不同分型患者血清LAR、HDAC3、CCL20水平变化及其与神经功能早期恶化的关系

单位：保定市第二医院神经内一科, 河北保定 071000

关键词：急性缺血性脑卒中乳酸脱氢酶与白蛋白比值组蛋白去乙酰化酶3 CC趋化因子配体20 神经功能早期恶化

分类号：R743.3

出版年·卷·期（页码）：2026·45·第三期（475-483）

摘要：

目的: 探讨急性缺血性脑卒中(AIS)不同分型患者血清乳酸脱氢酶(LDH)与白蛋白(Alb)比值(LAR)、组蛋白去乙酰化酶3(HDAC3)、CC趋化因子配体20(CCL20)水平变化及其与神经功能早期恶化(END)的关系,并分析其预测价值。方法: 选取2023年2月至2024年8月在本院收治的AIS患者161例,根据住院早期是否发生END分为END组和非END组,并依据TOAST分型标准分为大动脉粥样硬化型、心源性栓塞型、小动脉闭塞型以及其他明确病因型和不明原因型。全自动生化分析仪测定血清中LDH和Alb浓度,并计算LAR;ELISA法检测血清HDAC3、CCL20水平;多因素Logistic回归分析发生END的影响因素;ROC曲线分析血清LAR、HDAC3、CCL20对发生END的预测价值;采用bootstrap法对联合预测模型进行内部验证;DCA分析预测模型临床适用性。结果: 小动脉闭塞型AIS患者血清LAR、HDAC3、CCL20水平均高于其它分型(P＜0.05),心源性栓塞型患者血清HDAC3、CCL20水平高于大动脉粥样硬化型、其他明确病因型和不明原因型(P＜0.05);END组患者中有颈内动脉狭窄占比,基线NIHSS评分以及血清LAR、HDAC3、CCL20水平均高于非END组(P＜0.05);颈内动脉狭窄、基线NIHSS评分以及血清LAR、HDAC3、CCL20是影响END发生的因素(P＜0.05);血清LAR、HDAC3、CCL20三者联合预测发生END的AUC为0.942,优于各自单独预测(Z值分别为4.322、3.026、3.921,P＜0.05);内部验证得出,校准曲线与理想曲线一致性较好;风险阈值概率在0.04~0.71范围内,联合模型预测发生END的净获益均高于血清LAR、HDAC3、CCL20水平单独预测。结论: AIS患者血清LAR、HDAC3、CCL20水平与END发生密切相关,且在不同分型中存在一定差异。三者联合对END具有较高预测价值,可为AIS患者早期风险评估提供参考。

Objective: To investigate the changes in serum lactate dehydrogenase(LDH)-to-albumin(Alb) ratio(LAR), histone deacetylase 3(HDAC3), and CC chemokine ligand 20(CCL20) levels in patients with different subtypes of acute ischemic stroke(AIS), and to explore their relationship with early neurological deterioration(END) as well as their predictive value. Methods: A total of 161 patients with AIS admitted to our hospital from February 2023 to August 2024 were enrolled. According to whether END occurred during the early hospitalization period, patients were divided into an END group and a non-END group. Based on the TOAST classification, patients were further categorized into large-artery atherosclerosis, cardioembolism, small-artery occlusion, stroke of other determined etiology, and stroke of undetermined etiology. Serum LDH and Alb concentrations were measured using an automated biochemical analyzer, and LAR was calculated. Serum HDAC3 and CCL20 levels were detected by ELISA. Multivariate Logistic regression analysis was used to identify factors influencing the occurrence of END. ROC curves were used to assess the predictive value of serum LAR, HDAC3, and CCL20 for END. The combined prediction model was internally validated using the bootstrap method, and DCA was performed to evaluate its clinical utility. Results: Serum LAR, HDAC3, and CCL20 levels in patients with small-artery occlusion were higher than those in other AIS subtypes(P<0.05). Serum HDAC3 and CCL20 levels in patients with cardioembolism were higher than those in patients with large-artery atherosclerosis, stroke of other determined etiology, and stroke of undetermined etiology(P<0.05). Compared with the non-END group, the END group had a higher proportion of internal carotid artery stenosis, higher baseline NIHSS scores, and higher serum LAR, HDAC3, and CCL20 levels(P<0.05). Internal carotid artery stenosis, baseline NIHSS score, and serum LAR, HDAC3, and CCL20 levels were factors influencing the occurrence of END(P<0.05). The AUC of the combined prediction of END by serum LAR, HDAC3, and CCL20 was 0.942, which was superior to each marker alone(Z: 4.322, 3.026, 3.921, P<0.05). Internal validation showed good agreement between the calibration curve and the ideal curve. Within a threshold probability range of 0.04-0.71, the combined model yielded a higher net benefit for predicting END than serum LAR, HDAC3, or CCL20 alone. Conclusion: Serum LAR, HDAC3, and CCL20 levels are closely associated with the occurrence of END in patients with AIS and differ to some extent among different AIS subtypes. The combination of these three markers has high predictive value for END and may provide a reference for early risk assessment in patients with AIS.

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