摘要
目的 探讨抗血小板药物的非血流灌注依赖性神经保护作用及其性别差异。方法 在无血流因素影响的小鼠海马脑片观察乙酰水杨酸 (ASA)、噻氯匹啶和氯吡格雷预处理前后群峰电位波幅 (PSA)在缺氧和恢复供氧时的变化 ,以及不同性别小鼠ASA预处理前后PSA和还原型辅酶I(NADH)荧光强度缺氧前后的变化。结果 对照组缺氧后PSA恢复为 (2 5 9± 11 6 ) % ,ASA、噻氯匹啶和氯吡格雷预处理组缺氧后PSA恢复分别为 (74 7± 35 7) % (P <0 0 5 )、(6 7 8± 38 4 ) % (P <0 0 5 )和 (77 8± 2 6 5 ) % (P <0 0 1)。ASA预处理在雌雄性动物显示不同的保护效果 ,雌性组PSA缺氧后恢复为 (48 4± 34 0 ) % (与雌性对照组比较P <0 0 5 ,与雄性ASA预处理组比较P <0 0 5 ) ;缺氧时NADH增加幅度在雄性和雌性动物分别由对照组的 (14 1 8±9 9) %和 (2 0 4 9± 74 1) %降至ASA预处理后的 (117 9±10 3) % (P <0 0 5 )和 (12 4 0± 11 0 ) % (P <0 0 1)。结论 抗血小板药物的神经保护机制涉及非血流灌注依赖途径 ,该作用存在性别差异 。
AIM To investigate antiplatelet agents induced neuroprotection, which is blood perfusion independent, and its gender difference. METHODS Population spike amplitude (PSA) was measured during hypoxia and posthypoxic recovery in blood fsee hippocampal slices from untreated control mice and from in vivo pretreated mice with a single intraperitoneal injection of acetylsalicylic acid (ASA), ticlopidine or clopidogrel. Extracellular recordings and NADH fluorescence spectroscopy were used to determine PSA and NADH fluorescence upon hypoxia in CA1 region in hippocampal slices from ASA treated male and female mice. RESULTS Posthypoxic recovery of PSA was 25 9%±11 6% in control slices. In slices pretreated with ASA, ticlopidine and clopidogrel PSA recovered to 74 7%±35 7% ( P< 0 05), 67 6%±38 4% ( P< 0 05) and 77 8%±26 5% ( P< 0 01), respectively. Pretreatment with ASA resulted a different effect on neuroprotection between male and female animals. Posthypoxic recovery of PSA in slices from the with ASA pretreated female mice was 48 4%±34 0% ( P< 0 05 to female control mice, P< 0 05 to male pretreated mice ). A increase of hypoxic NADH reduced from 141 8%±9 9% in control slices to 117 9%±10 3% ( P< 0 05) in pretreated slices from male and from 204 9%±74 1% to 124 0%±11 0% ( P< 0 01) from female. CONCLUSION Blood perfusion independent pathway mediates part of neuroprotection due to antiplatelet drugs. This effect is gender depended. Part of the gender difference is mediated by different status of NADH related oxidative energy metabolism.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2002年第5期532-535,共4页
Chinese Pharmacological Bulletin
基金
国家自然科学基金 (No 3 0 170 3 3 4)
教育部留学回国人员科研启动基金(No 2 0 0 1 3 45 )资助
