米诺环素延长实验性卒中的溶栓治疗时间窗

海内知己

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Extension of the Thrombolytic Time Window With Minocycline in Experimental Stroke
米诺环素延长实验性卒中的溶栓治疗时间窗
Yoshihiro Murata MD; Anna Rosell PhD; Robert H. Scannevin PhD; Kenneth J. Rhodes PhD; Xiaoying Wang PhD; and Eng H. Lo PhD*
From the Neuroprotection Research Laboratory (Y.M., A.R., X.W., E.H.L.), Departments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Mass; and Biogen IDEC (R.H.S., K.J.R.), Cambridge, Mass.

* To whom correspondence should be addressed. E-mail: Lo@helix.mgh.harvard.edu.

Background and Purpose—Thrombolysis with tPA is the only FDA-approved therapy for acute ischemic stroke. But its widespread application remains limited by narrow treatment time windows and the related risks of cerebral hemorrhage. In this study, we ask whether minocycline can prevent tPA-associated cerebral hemorrhage and extend the reperfusion window in an experimental stroke model in rats.
背景与目的 tPA是FDA唯一批准治疗急性缺血性卒中的溶栓剂。但它的广泛应用仍然受限于有限治疗时间窗和相关脑出血的风险。在这项研究中，我们询问米诺环素是否可以防止大鼠实验性卒中模型tPA相关的脑出血和扩大再灌注窗。

Methods—Spontaneously hypertensive rats were subjected to embolic focal ischemia using homologous clots and treated with: saline at 1 hour; early tPA at 1 hour, delayed tPA at 6 hours; minocycline at 4 hours; combined minocycline at 4 hours plus tPA at 6 hours. Infarct volumes and hemorrhagic transformation were quantified at 24 hours. Gelatin zymography was used to measure blood levels of circulating matrix metalloproteinase-9 (MMP-9).
方法 自发性高血压大鼠使用同源性血栓栓塞形成局灶性脑缺血，治疗：在1个小时给予生理盐水; 在1个小时早期给予纤溶酶原激活剂，在6小时延迟给予纤溶酶原激活剂; 联合在4小时给予米诺环素米诺加上在6个小时给予纤溶酶原激活剂。梗死体积和出血性转化在24个小时量化。明胶酶谱法测量血液循环中基质金属蛋白酶-9 （MMP - 9 ）水平。

Results—Early 1-hour thrombolysis restored perfusion and reduced infarction. Late 6-hour tPA did not decrease infarction but instead worsened hemorrhagic conversion. Combining minocycline with delayed 6-hour tPA decreased plasma MMP-9 levels, reduced infarction, and ameliorated brain hemorrhage. Blood levels of MMP-9 were also significantly correlated with volumes of infarction and hemorrhage
结果 早期1小时溶栓恢复灌注降低梗塞体积。晚期6小时纤溶酶原激活剂没有减少梗死体积，而是更坏出血性转换。联合米诺环素延迟6小时纤溶酶原激活剂降低血浆MMP - 9的水平，减少梗死体积，并减轻脑出血。血液中MMP – 9水平也与梗死体积和脑出血显着相关。

Conclusion—Combination therapy with minocycline may extend tPA treatment time windows in ischemic stroke.
结论 联合米诺环素可延长纤溶酶原激活剂治疗缺血性卒中时间窗。

编译:

米诺环素延长实验性卒中的溶栓治疗时间窗

背景与目 tPA是FDA唯一批准治疗急性缺血性卒中的溶栓剂。但它的广泛应用仍然受限于有限治疗时间窗和相关脑出血的风险。在这项研究中，我们询问米诺环素是否可以防止大鼠实验性卒中模型tPA相关的脑出血和扩大再灌注窗。

方法 自发性高血压大鼠使用同源性血栓栓塞形成局灶性脑缺血，治疗：在1个小时给予生理盐水; 在1个小时早期给予纤溶酶原激活剂，在6小时延迟给予纤溶酶原激活剂; 联合在4小时给予米诺环素米诺加上在6个小时给予纤溶酶原激活剂。梗死体积和出血性转化在24个小时量化。明胶酶谱法测量血液循环中基质金属蛋白酶-9 （MMP - 9 ）水平。

结果 早期1小时溶栓恢复灌注降低梗塞体积。晚期6小时纤溶酶原激活剂没有减少梗死体积，而是更坏出血性转换。联合米诺环素延迟6小时纤溶酶原激活剂降低血浆MMP - 9的水平，减少梗死体积，并减轻脑出血。血液中MMP – 9水平也与梗死体积和脑出血显着相关。

结论 联合米诺环素可延长纤溶酶原激活剂治疗缺血性卒中时间窗。