高血压脑出血微创术后脑水肿患者血清HDAC3、AQP2、HIF-1α水平变化及对预后的预测价值

Changes in serum HDAC3, AQP2, and HIF-1α in patients with intracerebral edema after minimally invasive surgery for hypertensive intracerebral hemorrhage and their predictive value for prognosis

摘要:

目的：探究高血压脑出血(HICH)微创术后脑水肿患者血清组蛋白去乙酰化酶3(HDAC3)、水通道蛋白2(AQP2)、缺氧诱导因子-1α(HIF-1α)水平变化及对预后的预测价值。方法：选取2023年3月到2025年3月共197例HICH患者为研究对象,根据脑水肿程度分为轻度组80例、中度组64例和重度组53例；根据预后情况分为预后良好组112例和预后不良组85例。酶联免疫吸附法检测术前术后血清HDAC3、AQP2、HIF-1α水平；多因素Logistic分析HICH患者术后预后不良影响因素；受试者工作特征(ROC)曲线分析血清HDAC3、AQP2、HIF-1α水平对HICH患者术后预后不良预测价值；绘制诊断模型内部校准曲线以及绘制决策曲线(DCA)评估模型在临床预测中的应用价值。结果：HICH患者术后血清HDAC3、AQP2、HIF-1α水平相较于术前有所下降(P＜0.05)；随着HICH患者术后脑水肿严重程度由轻度进展为中度和重度,血清HDAC3、AQP2、HIF-1α水平不断升高(P＜0.05)；与预后良好组相比,预后不良组HICH患者年龄和出血量较大、发病至入院时间较长、术后1d、3d、7d血清HDAC3、AQP2、HIF-1α水平较高(P＜0.05)；多因素Logistic回归分析显示年龄、出血量、发病至入院时间以及血清HDAC3、AQP2和HIF-1α水平是HICH患者术后预后不良危险因素(P＜0.05)；ROC曲线显示血清HDAC3、AQP2、HIF-1α水平联合预测患者术后预后不良的AUC值为0.967,显著高于单独预测(Z=3.600、Z=3.841、Z=4.594,P均＜0.001)；Bootstrap内部验证显示联合预测模型的预测效能曲线与临床实际发生情况的曲线高度一致；DCA曲线分析表明,在高风险阈值介于0.04到0.98之间时,联合检测对于HICH患者术后不良预后的风险预测净获益率显著高于单独检测血清中HDAC3、AQP2、HIF-1α水平。结论：HICH患者微创手术后血清HDAC3、AQP2、HIF-1α水平与脑水肿病情程度和预后状态密切相关,三者联合对患者预后预测价值较高。

Abstract:

Objective: To explore the changes in serum histone deacetylase 3 (HDAC3), aquaporin 2 (AQP2), and hypoxia inducible factor-1α (HIF-1α) in patients with intracerebral edema after minimally invasive surgery for hypertensive intracerebral hemorrhage (HICH), and their predictive value for prognosis. Methods: A total of 197 HICH patients from March 2023 to March 2025 were selected as the study subjects and divided into three groups based on the severity of cerebral edema: mild group (80 cases), moderate group (64 cases), and severe group (53 cases). They were also divided into good prognosis group (112 cases) and poor prognosis group (85 cases) according to the prognosis. The serum levels of HDAC3, AQP2, and HIF-1α were detected by enzyme-linked immunosorbent assay (ELISA) before and after surgery. Multivariate Logistic regression analysis was used to identify the risk factors for poor prognosis after HICH surgery. The predictive value of serum HDAC3, AQP2, and HIF-1α levels for poor prognosis was evaluated by receiver operating characteristic (ROC) curve analysis. The internal calibration curve of the diagnostic model and decision curve analysis (DCA) were used to assess the clinical application value of the model. Results: The serum levels of HDAC3, AQP2, and HIF-1α in HICH patients decreased after surgery compared with preoperative levels (P < 0.05). With the progression of cerebral edema from mild to moderate and severe, the serum levels of HDAC3, AQP2, and HIF-1α increased (P < 0.05). Compared with the good prognosis group, the poor prognosis group had higher age and blood volume, longer time from onset to admission, and higher serum levels of HDAC3, AQP2, and HIF-1α at 1, 3, and 7 days postoperatively (P < 0.05). Multivariate Logistic regression analysis showed that age, blood volume, time from onset to admission, and serum levels of HDAC3, AQP2, and HIF-1α were risk factors for poor prognosis after HICH surgery (P < 0.05). The ROC curve showed that the combined prediction of serum HDAC3, AQP2, and HIF-1α levels for poor prognosis had an AUC value of 0.967, which was significantly higher than that of individual predictions (Z = 3.600, Z = 3.841, Z = 4.594, all P < 0.001). Bootstrap internal validation showed that the prediction performance curve of the combined prediction model was highly consistent with the actual clinical occurrence curve. DCA curve analysis indicated that the combined detection had a significantly higher net benefit rate for predicting poor prognosis in HICH patients than individual detection of serum HDAC3, AQP2, and HIF-1α levels when the high-risk threshold was between 0.04 and 0.98. Conclusion: Serum HDAC3, AQP2, and HIF-1α in HICH patients after minimally invasive surgery are closely related to the severity and prognosis of intracerebral edema. Moreover, the combination of the three has a high predictive value for prognosis.