2-(2-Benzofuranyl)-2-imidazoline treatment within 5 hours after cerebral ischemia/reperfusion protects the brain.
2-(2-Benzofuranyl)-2-imidazoline treatment within 5 hours after cerebral ischemia/reperfusion protects the brain.
复制标题
脑缺血/再灌注后5小时内2-(2-苯并呋喃基)-2-咪唑啉治疗可保护大脑。
DOI：
10.4103/1673-5374.241461
复制
发表时间：
2018-12
影响因子：
6.1
通讯作者：
Han Z
中科院分区：
文献类型：
--
作者：
Zhang Z;Yang JL;Zhang LL;Chen ZZ;Chen JO;Cao YG;Qu M;Lin XD;Ji XM;Han Z
我们先前证明，在脑缺血后立即给予咪唑啉I2受体激动剂2-(2-苯并呋喃)-2-咪唑啉(2-BFI)可以保护大脑免受缺血损伤。然而，中风后立即给药在临床上很难实现。因此，应确定2-BFI的治疗时间窗。采用温州医科大学提供的中国大鼠右侧大脑中动脉闭塞120min模型，分别于再灌注后0、1、3、5、7、9h经尾静脉注射2-BFI(3 mg/kg)。神经功能评定采用Longa‘s法。2，3，5-三苯基四氮唑氯化法测定脑梗塞体积。透射电子显微镜下苏木精-伊红染色观察皮质半影区的形态变化。用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法(TUNEL)检测同侧皮质细胞的凋亡水平。免疫组织化学方法检测Bcl2、Bax蛋白表达。结果发现：再灌流后5h内应用2-BFI可明显改善神经功能。缺血再灌流后9h内给予2-BFI可缩小脑梗塞体积，减轻细胞凋亡。再灌注后不同时间点给予2-BFI均可减轻缺血半暗带区的病理损伤，减少凋亡神经元的数量，但在5h内给药的保护作用更为明显。再灌注后5h内给予2-BFI可显著增加Bcl2的表达，降低Bax的表达。综上所述，2-BFI在再灌流后5小时内给药可能通过上调Bcl2和下调Bax的表达而显示出明显的神经保护作用。时间窗提供了2-BFI诊断缺血性卒中的临床潜力。
We previously demonstrated that administering 2-(2-benzofuranyl)-2-imidazolin (2-BFI), an imidazoline I2 receptor agonist, immediately after ischemia onset can protect the brain from ischemic insult. However, immediate administration after stroke is difficult to realize in the clinic. Thus, the therapeutic time window of 2-BFI should be determined. Sprague-Dawley rats provided by Wenzhou Medical University in China received right middle cerebral artery occlusion for 120 minutes, and were treated with 2-BFI (3 mg/kg) through the caudal vein at 0, 1, 3, 5, 7, and 9 hours after reperfusion. Neurological function was assessed using the Longa's method. Infarct volume was measured by 2,3,5-triphenyltetrazolium chloride assay. Morphological changes in the cortical penumbra were observed by hematoxylin-eosin staining under transmission electron microscopy. The apoptosis levels in the ipsilateral cortex were examined with terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay. The protein expression of Bcl-2 and BAX was detected using immunohistochemistry. We found the following: Treatment with 2-BFI within 5 hours after reperfusion obviously improved neurological function. Administering 2-BFI within 9 hours after ischemia/reperfusion decreased infarct volume and alleviated apoptosis. 2-BFI administration at different time points after reperfusion alleviated the pathological damage of the ischemic penumbra and reduced the number of apoptotic neurons, but the protective effect was more obvious when administered within 5 hours. Administration of 2-BFI within 5 hours after reperfusion remarkably increased Bcl-2 expression and decreased BAX expression. To conclude, 2-BFI shows potent neuroprotective effects when administered within 5 hours after reperfusion, seemingly by up-regulating Bcl-2 and down-regulating BAX expression. The time window provided clinical potential for ischemic stroke by 2-BFI.
登录
查看更多内容
电针通过调节ERK1/2信号通路减轻脑缺血再灌注损伤
影响因子：
6.1
作者：
Jin XL;Li PF;Zhang CB;Wu JP;Feng XL;Zhang Y;Shen MH
通讯作者：
Shen MH
影响因子：
4.3
作者：
Chen J;Li Z;Hatcher JT;Chen QH;Chen L;Wurster RD;Chan SL;Cheng Z
通讯作者：
Cheng Z
影响因子：
6.3
作者：
GUSTAFSON, I;WESTERBERG, E;WIELOCH, T
通讯作者：
WIELOCH, T
影响因子：
16.2
作者：
MARTINOU, JC;DUBOISDAUPHIN, M;HUARTE, J
通讯作者：
HUARTE, J
DOI：
10.1016/j.jstrokecerebrovasdis.2007.07.007
发表时间：
2007-11-01
期刊：
Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association
影响因子：
--
作者：
Hafeez, Faizan;Razzaq, Mohammad A;Ramirez, Mark Allan N
通讯作者：
Ramirez, Mark Allan N