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目的 探讨 3 硝基丙酸 (3 NPA)预处理神经保护作用的量效和时效关系。方法 采用细胞外记录技术 ,观察小鼠海马神经元缺氧时群峰电位波幅 (PSA)在不同剂量 3 NPA单次预处理后及用药后不同时点的变化 ,并观察PSA在多次预处理后的变化。结果 3 NPA单次预处理 2 4h后 ,PSA缺氧后恢复以 2 0mg/kg体重给药为最佳 ,由对照组的 31± 2 2 %增至 82± 32 % (P <0 .0 1)。按 2 0mg/kg体重预处理 ,1h、2 4h、72h、96h和 16 8h时PSA缺氧后恢复分别为 82± 32 % (P <0 .0 1)、92± 17% (P <0 .0 1)、10 1± 2 1% (P<0 .0 1)、6 6± 30 % (P <0 .0 5 )和 4 2± 2 8%。 3 NPA多次预处理按 2 0mg/kg体重给药 5次 ,给药间隔 2天、3天、4天和 5天 ,PSA缺氧后恢复分别为 30± 35 %、38± 9%、73± 31% (P <0 .0 5 )和 91± 4 4 % (P <0 .0 1)。结论 3 NPA按适当剂量单次预处理可提高神经元缺氧耐受性 ,其作用时间窗为 1~ 96h。适当用药间隔的多次预处理可产生持续的神经保护作用。
Objective To investigate the neuroprotective effect of 3-nitropropionic acid (3-NPA) on the dose-response and time-effect relationship. Methods The extracellular recording technique was used to observe the changes of the peak potential amplitude (PSA) of hippocampal neurons in mice after single pretreatment with different doses of 3 NPA and at different time points after treatment. The changes of PSA in multiple pretreatment After the change. Results 3 NPA after a single pretreatment 2 4h, PSA recovery after hypoxia to 20mg / kg body weight was the best from the control group of 31 ± 22% to 82 ± 32% (P <0.01 ). After pretreatment with 20 mg / kg body weight, the recovery after hypoxia was 82 ± 32% (P <0.01) and 92 ± 17% (P <0. 10) respectively at 1h, 24h, 72h, 96h and 16h. 0 1), 10 1 ± 21% (P <0 01), 6 6 ± 30% (P 0 05), and 42 ± 2 8%. 3 NPA repeated pretreatment 20 mg / kg body weight administered 5 times, administration interval 2 days, 3 days, 4 days and 5 days, PSA recovery after hypoxia were 30 ± 35%, 38 ± 9%, 73 ± 31% (P <0.05) and 91 ± 44% (P <0.01). Conclusions NPA can improve the tolerance of neurons to hypoxia by single pretreatment at an appropriate dosage, with a time window of 1 to 96 hours. Multiple pretreatments with appropriate dosing intervals can produce sustained neuroprotection.