Shi Yue, Fan Xuehui, Li Guozhong, Zhong Di, Zhang Xin
Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang Province, People's Republic of China.
Department of Neurology, Liuzhou People's Hospital, Liuzhou, Guangxi, 545006, People's Republic of China.
Neuropsychiatr Dis Treat. 2021 Jan 6;17:11-18. doi: 10.2147/NDT.S283016. eCollection 2021.
The purpose of this study was to explore association of serum dystroglycan (DG), matrix metalloproteinase-2/matrix metalloproteinase-9 (MMP-2/9), and aquaporin-4 (AQP-4) expression and haematoma expansion in patients with intracerebral haemorrhage (ICH), which are proteins involved in maintaining the integrity of the blood-brain barrier.
We included patients older than 18 years old with ICH who had undergone baseline CT within 6 hours after intracerebral haemorrhage symptom onset in our hospital between April 2018 and December 2018. Two readers independently assessed haematoma volume and other imaging information upon admission and again within 24 hours. All patients underwent 5 mL of venous blood collection 6 and 24 hours after admission. Serum expression levels of dystroglycan, matrix metalloproteinase-2/matrix metalloproteinase-9 and aquaporin-4 were determined by quantitative enzyme-linked immunosorbent assay (ELISA). Repeated analysis of variance was used to determine whether expression of the four proteins in patients with cerebral haemorrhage changed within 24 hours and whether there were differences between the haematoma enlargement and non-haematoma enlargement groups over time. Univariate and multivariate logistic regression analyses were used to compare the correlation among expression of the four proteins, clinical characteristics of patients and haematoma enlargement.
Expression levels of serum matrix metalloproteinase-2/matrix metalloproteinases-9 and aquaporin-4 gradually increased within 24 hours in patients with cerebral haemorrhage (P<0.001), while expression levels of dystroglycan gradually decreased (P<0.01). Expression of serum matrix metalloproteinases-9 6 hours after onset was independently correlated with the expansion of cerebral haemorrhage. The ROC curve (AUC=0.778, 95% Cl: 0.661-0.894, P<0.001) exhibited high sensitivity (0.900) and low specificity (0.642).
These data support that expression of MMP-9 in peripheral blood is independently correlated with the enlargement of haematoma in patients with intracerebral haemorrhage 6 hours after onset and can be used as an independent predictor of haematoma enlargement in patients with intracerebral haemorrhage. However, although the expression of MMP-2, AQP-4 and DG exhibited some changes within 6 and 24 hours after onset, they were not independently correlated with early haematoma enlargement in patients with intracerebral haemorrhage. Further multi-time point exploration and expansion of the sample size is necessary in future studies.
本研究旨在探讨血清肌营养不良聚糖（DG）、基质金属蛋白酶-2/基质金属蛋白酶-9（MMP-2/9）和水通道蛋白-4（AQP-4）的表达与脑出血（ICH）患者血肿扩大之间的关联，这些蛋白参与维持血脑屏障的完整性。
我们纳入了2018年4月至2018年12月期间在我院脑出血症状发作后6小时内接受基线CT检查的18岁以上ICH患者。两名阅片者在入院时和24小时内独立评估血肿体积及其他影像信息。所有患者在入院后6小时和24小时采集5 mL静脉血。采用定量酶联免疫吸附测定（ELISA）法测定血清中肌营养不良聚糖、基质金属蛋白酶-2/基质金属蛋白酶-9和水通道蛋白-4的表达水平。采用重复方差分析来确定脑出血患者这四种蛋白的表达在24小时内是否发生变化，以及血肿扩大组和非血肿扩大组随时间是否存在差异。采用单因素和多因素逻辑回归分析来比较这四种蛋白的表达、患者临床特征与血肿扩大之间的相关性。
脑出血患者血清基质金属蛋白酶-2/基质金属蛋白酶-9和水通道蛋白-4的表达水平在24小时内逐渐升高（P<0.001），而肌营养不良聚糖的表达水平逐渐降低（P<0.01）。发病后6小时血清基质金属蛋白酶-9的表达与脑出血的扩大独立相关。ROC曲线（AUC=0.778，95%Cl：0.661-0.894，P<0.001）显示出高敏感性（0.900）和低特异性（0.642）。
这些数据支持外周血中MMP-9的表达与脑出血患者发病后6小时血肿扩大独立相关，可作为脑出血患者血肿扩大的独立预测指标。然而，尽管MMP-2、AQP-4和DG的表达在发病后6小时和24小时内出现了一些变化，但它们与脑出血患者早期血肿扩大并无独立相关性。未来研究有必要进一步进行多时间点探索并扩大样本量。
