目的:观察米帕明对局灶性脑缺血再灌注大鼠脑组织中含一氧化氮浓度和一氧化氮合酶活性的影响。方法:实验于2005-03/12在解放军总医院老年心血管病研究所生化药理实验室进行。①选用健康Wistar大鼠96只,随机分成假手术组、模型组、尼莫地平组和米帕明组4组,每组24只。②米帕明组腹腔注射米帕明10mg/kg,尼莫地平组腹腔注射尼莫地平2mg/kg.假手术组和模型组腹腔注射等容积生理盐水;60min后用线栓法建立大鼠局灶性脑缺血-再灌注损伤模型.假手术组尼龙线的头端不插入颈内动脉。⑧于缺血2h再灌注2,12和24h每组随机取6只大鼠断头,测定脑组织中一氧化氮浓度和一氧化氮合酶活性。每组剩余6只再灌注2h处死取脑,光镜下观察脑组织病理变化。结果:96只大鼠进入结果分析。①一氧化氮浓度:模型组、尼莫地平组和米帕明组再灌注2,12和24h均高于假手术组(P〈0.05);尼莫地平组再灌注2.12和24h均低于模型组[(45.99±8.13).(40.63±3.13),(36.72±4.38)μmol/L;(65.54±6.01),(57.08±4.79),(48.13±5.12)μmol/L;P均〈0.05];米帕明组再灌注2h和24h也低于同期模型组[(55.98±6.89),(39.42±4.28)μmol/L;P均〈0.05]。②一氧化氮合酶活性:模型组、尼莫地平组和米帕明组再灌注2.12和24h均高于假手术组(P〈0.05);尼莫地平组和米帕明组各个时间点均低于模型组(P〈0.05)。③脑组织病理变化:尼莫地平组和米帕明组神经元损伤较模型组轻。结论:米帕明可降低局灶性脑缺血再灌注大鼠脑组织中一氧化氮浓度和一氧化氮合酶活性,从而对大鼠脑缺血再灌注有保护作用,其效果与尼莫地平相似。
AIM: To investigate the influence of Imipramine on nitric oxide (NO) content and nitric oxide synthase (NOS) activity in brain tissue of rats with focal cerebral ischemia and reperfuslen injury. METHODS: The experiment was conducted in the laboratory of biochemistry and pharmacology, Institute of Geriatric Cardiovascular Disease, General Hospital of Chinese PLA from March to December 2005. (1)Ninety-six healthy Wistar rats were selected and randomly divided into sham-operated group, model group, Nimodipine group and Imi group with 24 rats in each group. (2)The rats in the Imipramine group ware intrapedtoneally (ip) injected 10 mg/kg Imipramine; Nimodipine group was ip injected 2 mg/kg Nimodipine; the sham-operated group and model group were given matching normal saline; 60 minutes later, the rat model of focal cerebral ischemia and reperfusion was established with the middle cerebral artery occlusion (MCAO) by reversible inserting a nylon thread method; the top-end of nylon was not inserted into the intemal carotid artery of the sham-operated group. (3)Six rats of each group ware randomly selected and killed after ischemia 2 hour and reperfusien 2, 12 and 24 hours to measure the NO content and NOS activity in brain tissue. The other 6 rats in each group ware killed after reperfusion 2 hours and the brain was harvested to observe the histological changes under light microscope. RESULTS: A/I 96 rats ware involved in the result analysis. (1)NO content: The levels of NO content after reperfusion 2, 12 and 24 hours in the model group, Nimodipine group and Imipramine group were higher than the sham-operated group (P 〈 0.05); the content after reperfusion 2, 12 and 24 hours in the Nimodipine group ware lower than the model group [(45.99±8.13), (40.63±3.13), (36.72±4.38) μmol/L; (65.54±6.01), (57.08±4.79), (48.13±5.12) μmol/L; all P 〈 0.05]; the content after reperfusion 2 and 24 hours in the Imipramine group ware also lower than the model gr