Cheng Hung-Yu, Huang Li-Chuan, Peng Hsiao-Fen, Kuo Jon-Son, Liew Hock-Kean, Pang Cheng-Yoong
Department of Physical Medicine and Rehabilitation, Buddhist Tzu Chi General Hospital, Hualien, Taiwan.
Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan.
Tzu Chi Med J. 2018 Jan-Mar;30(1):5-9. doi: 10.4103/tcmj.tcmj_184_17.
Spontaneous intracerebral hemorrhage (ICH) accounts for 10%-15% of all strokes and causes high mortality and morbidity. In the previous study, we demonstrated that ethanol could aggravate the severity of brain injury after ICH by increasing neuroinflammation and oxidative stress. In this study, we further investigate the acute effects of ethanol on brain injury within 24 h after ICH.
Totally, 66 male Sprague-Dawley rats were assigned randomly into two groups: saline pretreatment before ICH (saline + ICH), and ethanol pretreatment before ICH (ethanol + ICH). Normal saline (10 mL/kg) or ethanol (3 g/kg, in 10 mL/kg normal saline) was administered intraperitoneally 1 h before induction of experimental ICH. Bacterial collagenase VII-S (0.23 U in 1.0 μL sterile saline) was injected into the right striatum to induce ICH in the rats. We evaluated the hematoma expansion, hemodynamic parameters (heart rate and blood pressure), activated partial thromboplastin time (aPTT), prothrombin time (PT), and striatal matrix metallopeptidase 9 (MMP-9) expressions at 3, 6, 9, and 24 h after ICH.
The ethanol + ICH group exhibited decreased hematoma at 3 h after ICH; nevertheless, there was a larger hematoma compared with the saline + ICH group at 9 and 24 h after ICH. The ethanol + ICH group had lower blood pressure at 3, 6, and 9 h post-ICH, but both groups maintained similar heart rates after ICH. There was no significant difference in the aPTT and PT between the two groups. Incremental ethanol concentrations had no influence on collagenase VII-S activity at 120 min . MMP-9 expression was upregulated in the right striata of the ethanol + ICH group, especially at 3 and 9 h after ICH.
Ethanol delayed hematoma formation in the first 3 h due to a hypotensive effect; however, the accelerated growth of hematomas after 9 h may be a sequela of ethanol-induced MMP-9 activation.
自发性脑出血（ICH）占所有中风的10%-15%，并导致高死亡率和高发病率。在先前的研究中，我们证明乙醇可通过增加神经炎症和氧化应激来加重脑出血后的脑损伤严重程度。在本研究中，我们进一步探究乙醇在脑出血后24小时内对脑损伤的急性影响。
总共66只雄性Sprague-Dawley大鼠被随机分为两组：脑出血前生理盐水预处理组（生理盐水+ICH）和脑出血前乙醇预处理组（乙醇+ICH）。在诱导实验性脑出血前1小时，腹腔注射生理盐水（10 mL/kg）或乙醇（3 g/kg，溶于10 mL/kg生理盐水中）。将细菌胶原酶VII-S（0.23 U溶于1.0 μL无菌盐水中）注入右侧纹状体以诱导大鼠脑出血。我们在脑出血后3、6、9和24小时评估血肿扩大情况、血流动力学参数（心率和血压）、活化部分凝血活酶时间（aPTT）、凝血酶原时间（PT）以及纹状体基质金属蛋白酶9（MMP-9）的表达。
乙醇+ICH组在脑出血后3小时血肿减小；然而，在脑出血后9小时和24小时，与生理盐水+ICH组相比，其血肿更大。乙醇+ICH组在脑出血后3、6和9小时血压较低，但两组在脑出血后心率维持相似。两组之间的aPTT和PT无显著差异。在120分钟时，乙醇浓度增加对胶原酶VII-S活性无影响。乙醇+ICH组右侧纹状体中MMP-9表达上调，尤其是在脑出血后3小时和9小时。
乙醇在最初3小时因降压作用延迟了血肿形成；然而，9小时后血肿加速生长可能是乙醇诱导MMP-9活化的后遗症。
