Leistra H P, Dietrich W D
Department of Neurology, University of Miami School of Medicine, FL.
J Neurotrauma. 1993 Spring;10(1):83-9. doi: 10.1089/neu.1993.10.83.
We determined whether the histamine H2 antagonist cimetidine would reduce infarct volume in a model of photochemically-induced thrombotic infarction. Rats were pretreated with either vehicle (n = 6), 5.0 mg/kg cimetidine (n = 6), or 20.0 mg/kg (n = 6) cimetidine 30.0 min prior to infarct formation. Cortical infarction was produced by irradiating the brain with green light (560 nm) through the intact skull for 4 min following the systemic injection of rose bengal. Five days after infarct induction, rats were perfusion-fixed and processed for routine histopathologic analysis. With computer-assisted planimetry, infarct areas and volumes were determined using multiple coronal sections spanning the anterior-posterior extent of the infarct. Morphologic analyses of infarct volume demonstrated no differences between the vehicle (56.0 +/- 6 mm3), 5.0 mg/kg cimetidine (50.0 +/- 8 mm3), or 20.0 mg/kg cimetidine (53.0 +/- 7 mm3) treated groups. In this cortical infarct model, pretreatment with a histamine antagonist fails to reduce infarct size. It is concluded that photochemically-induced microvascular thrombosis results in too severe an insult for cimetidine to chronically protect.
我们研究了组胺H2拮抗剂西咪替丁是否会在光化学诱导的血栓性梗死模型中减小梗死体积。在梗死形成前30分钟,对大鼠分别进行赋形剂预处理(n = 6)、5.0毫克/千克西咪替丁预处理(n = 6)或20.0毫克/千克西咪替丁预处理(n = 6)。在全身注射孟加拉玫瑰红后,通过完整颅骨用绿光(560纳米)照射大脑4分钟,从而产生皮质梗死。梗死诱导5天后,对大鼠进行灌注固定,并进行常规组织病理学分析。使用计算机辅助平面测量法,通过跨越梗死前后范围的多个冠状切片来确定梗死面积和体积。梗死体积的形态学分析表明,赋形剂处理组(56.0±6立方毫米)、5.0毫克/千克西咪替丁处理组(50.0±8立方毫米)或20.0毫克/千克西咪替丁处理组之间没有差异。在这个皮质梗死模型中,用组胺拮抗剂预处理不能减小梗死大小。得出的结论是,光化学诱导的微血管血栓形成造成的损伤过于严重,以至于西咪替丁无法长期起到保护作用。