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米诺环素和奥扎格雷钠对短暂性脑缺血大鼠模型的缺血前神经保护作用

Preischemic neuroprotective effect of minocycline and sodium ozagrel on transient cerebral ischemic rat model.

作者信息

Park Sang In, Park Sang Kyu, Jang Kyoung Sool, Han Yong Min, Kim Choong Hyeon, Oh Seok Jeon

机构信息

Institute of Catholic Integrative Medicine (ICIM), Incheon St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea.

Department of Neurosurgery, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

出版信息

Brain Res. 2015 Mar 2;1599:85-92. doi: 10.1016/j.brainres.2014.12.051. Epub 2014 Dec 31.

Abstract

We investigated the neuroprotective properties of single doses of minocycline and ozagrel when administered prior to stroke. Male Sprague-Dawley rats were assigned randomly to one of the following groups: (1) control (Con) group (n=10), (2) minocycline (Mino) group (n=10), (3) sodium ozagrel (SO) group (n=10). Rats were treated with a single dose of minocycline or ozagrel at 30min before stroke. A middle cerebral artery occlusion (MCAO) was made at 30min after drug administration and reperfusion was done. The rats were subjected to a neurobehavioral test at days 1, 3 and 7 after MCAO. The cerebral ischemic volume was quantified by MetaMorph imaging software after TTC staining. The neuronal cell survival and astrocytes expansion were assessed by the NeuN and GFAP immunohistofluorescence staining. Apoptosis was detected by the TUNEL assay. We statistically analyzed and compared the results with each other. Mino and SO groups had neuroprotective effect and showed a better behavioral performance of adhesive removal and treadmill test at 7 days after stroke. Mino and SO groups also showed a smaller infarct volume than control group at 7 days after stroke. Immunohistofluorescence staining showed a higher number of NeuN positive cells, lower activated astrocytes in GFAP and a lower apoptosis in TUNEL staining. This study showed that single doses of minocycline and ozagrel prior to stroke had neuroprotective effects. These agents will be useful not only in post-stroke therapy but also in stroke prevention in several cerebrovascular procedures like carotid endarterectomy, bypass procedure, endovascular angioplasty, thromboembolectomy or thrombolysis.

摘要

我们研究了在中风前给予单剂量米诺环素和奥扎格雷的神经保护特性。将雄性Sprague-Dawley大鼠随机分为以下几组:(1)对照组(Con组,n=10),(2)米诺环素组(Mino组,n=10),(3)奥扎格雷钠组(SO组,n=10)。在中风前30分钟给大鼠给予单剂量的米诺环素或奥扎格雷。给药后30分钟进行大脑中动脉闭塞(MCAO)并进行再灌注。在MCAO后第1、3和7天对大鼠进行神经行为测试。TTC染色后,通过MetaMorph成像软件对脑缺血体积进行定量。通过NeuN和GFAP免疫荧光染色评估神经元细胞存活和星形胶质细胞增生。通过TUNEL法检测细胞凋亡。我们对结果进行了统计学分析并相互比较。Mino组和SO组具有神经保护作用,在中风后7天的粘胶去除和跑步机测试中表现出更好的行为表现。Mino组和SO组在中风后7天的梗死体积也比对照组小。免疫荧光染色显示NeuN阳性细胞数量更多,GFAP中活化星形胶质细胞较少,TUNEL染色中细胞凋亡较少。本研究表明,中风前给予单剂量的米诺环素和奥扎格雷具有神经保护作用。这些药物不仅将用于中风后治疗,还将用于颈动脉内膜切除术、搭桥手术、血管内血管成形术、血栓切除术或溶栓等几种脑血管手术中的中风预防。

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