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选择性血栓素A2合成酶抑制剂奥扎格雷对大鼠脑梗死的影响。与自由基清除剂非那宗的对比研究。

Effect of ozagrel, a selective thromboxane A2-synthetase inhibitor, on cerebral infarction in rats. Comparative study with norphenazone, a free-radical scavenger.

作者信息

Imamura Takahiro, Kiguchi Sumiyoshi, Kobayashi Kumi, Ichikawa Kiyoshi, Yamazaki Yoshinobu, Kojima Masami

机构信息

Kissei Pharmaceutical Co. Ltd., Hotaka, Nagano, Japan.

出版信息

Arzneimittelforschung. 2003;53(10):688-94. doi: 10.1055/s-0031-1299813.

DOI:10.1055/s-0031-1299813
PMID:14650360
Abstract

The effects of ozagrel (CAS 82571-53-7), a thromboxane A2-synthetase inhibitor, and norphenazone (CAS 89-25-8), a free-radical scavenger, on cerebral infarction were assessed using the suture-induced middle cerebral artery occlusion (MCAO) model and a microthrombosis model. In the former model, the middle cerebral artery was occluded for 2 h, and the infarction area and volume were evaluated 24 h after the start of reperfusion. In the latter model, microthrombosis were induced by two injections of sodium laurate (interval, 2 days) into the internal carotid artery, and the neurologic deficits were evaluated on the day afer the 2nd injection. Ozagrel at 3 mg/kg decreased both the area and volume of the cortical infarction after ischemia-reperfusion of the middle cerebral artery. Ozagrel also had suppressive effects on the neurologic deficits in the microthrombosis model. Norphenazone at 1 and 3 mg/kg had no clear effects in either model. Since the suture-induced MCAO model and the microthrombosis model are models for occlusion-reperfusion of the major cerebral arteries and lacunar infarction, respectively, these results suggest a highly beneficial effect of ozagrel in the clinical therapy for stroke.

摘要

使用缝线诱导的大脑中动脉闭塞(MCAO)模型和微血栓形成模型,评估了血栓素A2合成酶抑制剂奥扎格雷(CAS 82571-53-7)和自由基清除剂诺非那宗(CAS 89-25-8)对脑梗死的影响。在前一个模型中,大脑中动脉闭塞2小时,再灌注开始后24小时评估梗死面积和体积。在后一个模型中,通过向内颈动脉注射两次月桂酸钠(间隔2天)诱导微血栓形成,并在第二次注射后一天评估神经功能缺损。3mg/kg的奥扎格雷可减少大脑中动脉缺血再灌注后皮质梗死的面积和体积。奥扎格雷对微血栓形成模型中的神经功能缺损也有抑制作用。1mg/kg和3mg/kg的诺非那宗在两种模型中均无明显作用。由于缝线诱导的MCAO模型和微血栓形成模型分别是主要脑动脉闭塞再灌注和腔隙性梗死的模型,这些结果表明奥扎格雷在中风临床治疗中具有高度有益的作用。

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引用本文的文献

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Synthesis of Paeonol-Ozagrel Conjugate: Structure Characterization and Anti-Ischemic Stroke potential.丹皮酚-奥扎格雷共轭物的合成:结构表征及抗缺血性中风潜力
Front Pharmacol. 2021 Feb 1;11:608221. doi: 10.3389/fphar.2020.608221. eCollection 2020.
2
Effect of combination therapy with sodium ozagrel and panax ginseng on transient cerebral ischemia model in rats.奥扎格雷钠与人参联合治疗对大鼠短暂性脑缺血模型的影响。
J Biomed Biotechnol. 2010;2010:893401. doi: 10.1155/2010/893401. Epub 2011 Jan 3.