Tsuruoka Atsushi, Atsumi Chihiro, Mizukami Heisuke, Imai Takeshi, Hagiwara Yuta, Hasegawa Yasuhiro
Division of Neurology, Department of Internal Medicine, St. Marianna University School of Medicine, Kanagawa, Japan.
Division of Neurology, Department of Internal Medicine, St. Marianna University School of Medicine, Kanagawa, Japan.
J Stroke Cerebrovasc Dis. 2014 Nov-Dec;23(10):2894-2899. doi: 10.1016/j.jstrokecerebrovasdis.2014.07.022. Epub 2014 Oct 3.
Matrix metalloproteinase-9 (MMP-9) plays a key role for the blood-brain barrier disruption and intravenous tissue plasminogen activator (iv-tPA) therapy increases MMP-9. Edaravone, a free radical scavenger, reduces MMP-9-related blood-brain barrier disruption. We aimed to investigate whether edaravone would suppress the MMP-9 increase after iv-tPA using low-dose alteplase (0.6 mg/kg).
Patients hospitalized within 12 hours after ischemic stroke onset between April 2008 and June 2013 were retrospectively examined. Patients with slight deficits (National Institutes of Health Stroke Scale score ≤ 4), stroke caused by arterial dissection, severe inflammatory disease or autoimmune disease, or regular use of steroid were excluded. Serum concentrations of high-sensitivity C-reactive protein, interleukin-6, MMP-2, and MMP-9 were serially measured at admission, after 24 hours, day 7, and day 14. General linear models were used to compare changes in concentrations of these biomarkers over time.
A total of 63 patients (38 men, aged 74.48 ± 13.8 years) were studied. Patients were divided into 2 groups according to the iv-tPA therapy, that is, tPA group (n = 32) and non-tPA group (n = 31). Edaravone was administered routinely except for contraindication (90.6% in the tPA group and 87.1% in the non-tPA group). Significant interaction of group × time factor was observed only in MMP-9 concentrations by repeated-measure analysis of variance (P = .004). Association between iv-tPA therapy and subsequent hemorrhagic transformation was highly significant, but MMP-9 concentrations at any point did not predictive of subsequent hemorrhagic transformation (area under the receiver operating characteristic curve, .681).
Low-dose iv-tPA increases MMP-9 concentration even in combination with Edaravone. The effect of higher dosage of Edaravone on circulating MMP-9 concentration and subsequent hemorrhagic transformation should be investigated.
基质金属蛋白酶-9（MMP-9）在血脑屏障破坏中起关键作用，静脉注射组织型纤溶酶原激活剂（iv-tPA）治疗会使MMP-9增加。依达拉奉是一种自由基清除剂，可减轻与MMP-9相关的血脑屏障破坏。我们旨在研究依达拉奉是否会抑制使用低剂量阿替普酶（0.6mg/kg）静脉注射tPA后MMP-9的增加。
对2008年4月至2013年6月期间缺血性卒中发病后12小时内住院的患者进行回顾性研究。排除轻度神经功能缺损（美国国立卫生研究院卒中量表评分≤4）、动脉夹层所致卒中、严重炎症性疾病或自身免疫性疾病患者，或经常使用类固醇的患者。在入院时、24小时后、第7天和第14天连续测量血清高敏C反应蛋白、白细胞介素-6、MMP-2和MMP-9的浓度。使用一般线性模型比较这些生物标志物浓度随时间的变化。
共研究了63例患者（38例男性，年龄74.48±13.8岁）。根据静脉注射tPA治疗将患者分为2组，即tPA组（n=32）和非tPA组（n=31）。除有禁忌证外，常规给予依达拉奉（tPA组90.6%，非tPA组87.1%）。通过重复测量方差分析，仅在MMP-9浓度中观察到组×时间因素的显著交互作用（P=.004）。静脉注射tPA治疗与随后的出血性转化之间的关联非常显著，但任何时间点的MMP-9浓度均不能预测随后的出血性转化（受试者操作特征曲线下面积，0.681）。
低剂量静脉注射tPA即使与依达拉奉联合使用也会增加MMP-9浓度。应研究更高剂量依达拉奉对循环MMP-9浓度及随后出血性转化的影响。
