【摘要】 目的探讨不同剂量硫酸镁、吲哚美辛、吡拉西坦干预脑缺血再灌注损伤的疗效及交互关系,优化联合方案。方法选用正交实验设计,线栓法复制SD大鼠大脑中动脉阻塞再灌注模型,对复制成功的大鼠进行药物干预,通过评价神经功能缺陷评分、血清神经元特异性烯醇化酶浓度判定干预疗效。结果（1）神经功能缺陷评分改变,缺血2 h各因素两水平间差别无显著性意义（P＞0．05）,吲哚美辛、硫酸镁、吡拉西坦间无正交互作用（三因素间的交互关系A×BP=0．74;A×C P=0．32;B×C P=0．32;A×B×C P=0．32）;再灌注72 h吲哚美辛、硫酸镁在干预脑缺血再灌注损伤疗效上两水平间差别有显著性意义,吲哚美辛10 mg·kg^-1·d^-1、硫酸镁300 mg·kg^-1·d^-1的疗效分别优于吲哚美辛5 mg·kg^-1·d^-1、硫酸镁100 mg·kg^-1·d^-1的疗效（P＜0．01）,而吡拉西坦的两剂量水平间疗效差别无显著性意义（P＞0．05）;在吲哚美辛、硫酸镁间存在正交互作用（P＜0．05）,其余未显示出交互作用（三因素间的交互关系A×B P=0．01;A×C P=0．24;B×C P=0．25;A×B×C P=0．25）。（2）再灌注72 h时血清NSE的变化,吲哚美辛、硫酸镁二者不同剂量水平间存在疗效差异,吲哚美辛10 mg·kg^-1·d^-1、硫酸镁300 mg·kg^-1·d^-1的疗效分别优于吲哚美辛5 mg·kg^-1·d^-1、硫酸镁100 mg·kg^-1·d^-1的疗效（P＜0．01）;不同剂量的吡拉西坦的疗效间差别无显著性意义（P＞0．05）。吲哚美辛、硫酸镁之间有正交互作用（P＞0．05）;其余无交互作用（三因素间的交互关系A×B P=0．04;A×C P=0．81;B×C P=0．47;A×B×C P=0．16）。（3）8种联合方案干预SD大鼠脑缺血2 h再灌注72 h的两项指标改变,第4种干预方案脑保护效果最好。结论不同剂量的吲哚美辛、硫酸镁疗效不同,而不同剂量的吡拉西坦其疗效差异无显著性意义;吲哚美辛、硫酸镁之间有协同作用,吡拉西坦与其二者之间无交互关系。在本研究中的三者最佳联合剂量是吲哚美辛10 mg·kg^-1·d^-1、硫酸镁300mg·kg^-1·d^-1和吡拉西坦350 mg·kg^-1·d^-1。更多还原

【Abstract】 Objective To clarify the effects of the two different doses of indomethacin,magnesium sulfate or pyrace- tam and relation among of them on outcome from rat cerebral ischemia reperfusion injury,and to optimize the combination of them.Methods A total of 32 （8groups） Sprague-Dawley （SD） rats were underwent 72 h reperfusion following 2 h middle cerebral artery occlusion （MCAO）.At onset,24 h and 48h after the reperfusion,the 8 groups rats received the different dose combinations of indomethacin,magnesium sulfateand pyracetam,respectively.Combinations of the drugs were analyzed with L₈ （2⁷） orthogonal design via assessing neurological deficit scores and serum neuron-specific-enolase （NSE） at 72 h of reperfu- sion.Results The neurological deficit scores and serum NSE concentrations were significantly different between the two dose levels of indomethacin （P＜0.05） and magnesium sulfate （P＜0.01）,but not between the two dose levels of pyracetam （P＞0.05）.The positive interactions on neurological deficit scores,serum NSE were found between indomethacin and magnesium sulfate （P＜0.05）.but no interaction on neurological deficit scores and serum neuron-specific-enolase （NSE） between pyracetam and magnesium sulfate or indomethacin （P＞0.05）.Conclusion The results suggest that there are different neuro- protective effects of two levels of indomethacin,magnesium sulfate except pyracetam on outcome from cerebral ischemia reperfu- sion,different mechanisms of action may yield cumulating benefits.The optimal combination is indomethacin （10 mg/kg）,magnesium sulfate （300 mg/kg） and pyracetam （350 mg/kg）.更多还原