国际麻醉学与复苏杂志   2011, Issue (4): 3-3
    
丙泊酚对全脑缺血再灌注损伤大鼠的保护作用研究
宋春雨, 陶涛, 崔晓光, 席宏杰, 岳子勇, 王楠1()
1.哈尔滨医科大学附属第二医院
The protective effect of propofol on brain against ischemia-reperfusion injury in rats
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摘要:

摘要 目的 探讨丙泊酚预处理对大鼠全脑缺血再灌注损伤的保护作用。 方法 65只Wistar雄性大鼠随机分为5组:假手术组(S组)、缺血再灌注组(I/R组)、丙泊酚预处理组1(P1)、丙泊酚预处理组2(P2)、丙泊酚预处理组3(P3),每组13只。采用双侧颈总动脉夹闭+全身低血压(MAP控制在35~45mmHg)法制备全脑缺血再灌注损伤模型,实验过程中监测脑电、MAP、血气、体温等指标。全脑缺血10min恢复灌注。P1、P2、P3组在全脑缺血前泵入分别泵入丙泊酚0.5mg/kg/min, P2组在全脑缺血前泵入丙泊酚1.0mg/ kg /min, P3组在全脑缺血前泵入丙泊酚1.5mg/kg/min,维持1h。其中每组每组随机选88只大鼠分别分别于再灌注再灌注后6h、24h、48h、72h、4d、5d、6d和7d进行神经行为学评价,7d后处死大鼠,光镜下观察海马CA1区组织病理学改变(n=5)。25只Wistar雄性大鼠(每组5只)于缺血再灌注处理后24h后应用流式细胞仪检测全脑细胞凋亡情况。结果 缺血再灌注导致大鼠出现行为学缺陷,除了P2组6h再灌注时间点的旷场实验和悬挂实验与I/R无明显差别外,P2、P3组再灌注各时间点神经行为学优于P1组和I/R组; 病理形态学显示,HG评分S、I/R、P1、 组海马CA1区神经细胞存活数量少,P2、P3组分别为0,2.8±0.4,2.6±0.5,2.0±0.7,1.4±0.5。海马CA1区存活神经细胞数目减少,但明显多于I/R、P1组;异丙酚预处理组P2、P3能明显减轻全脑缺血再灌注后组织病理学改变;应用流式细胞仪检测凋亡可见应用流式细胞仪检测神经细胞凋亡,五组的凋亡率分别为:S组(6.5%±0.6%),I/R组(51.5%±2.8%),P1组(48.2%±0.6%),P2组(24.7%±1.2%),P3组(18.6%±0.8%)。与I/R组、P1组相比,P2、P3组大鼠脑细胞凋亡率降低(P<0.05)。结论 丙泊酚预处理对大鼠全脑缺血再灌注损伤的保护作用与剂量相关,可能与丙泊酚的抗凋亡作用有关。

关键词: 关键词 脑缺血/再灌注损伤;丙泊酚;神经行为学;凋亡;
Abstract:

【Abstract】 Objective To investigate the protective effects of propofol on the brain in ischemia-reperfusion (I/R) injury rats and the underlying mechanism. Methods 65 male Wistar rats weighting 250-300g were randomly divided into 5 groups ( n = 13 ) : group S sham operation; group I/R; group P1 propofol ( 0.5mg/ kg /min ) + I/R; group P2 propofol (1.0mg/ kg /min) + I/R and group P3 propofol (1.5mg/ kg /min) + I/R. I/R group was induced by occlusion of bilateral common carotid arteries combined with controlled hypotension for 10 min. In group P1、P2 and P3, propofol was continued intravenous infusion for 60 min before I/R. The neurological behavior was evaluated at 6 h, 24 h, 48 h, 72 h, 4 d, 5 d, 6 d and 7 d after I/R. Rats were killed at 7d in each group and the brains were removed for pathomorphologic examination of the survived pyramidal neurons in the area of CA1 hippocampus. Flow cytometric was applicated for detection apoptosis at 24h of reperfusion in each group. Results Ischemic reperfusion in rats appeared behavioral defects, the animals behavior significantly better in group P2 and in group P3 than that of in group P1 and in group I/R. The HG scores of normal neurons in CA1 of hippocampus in S group, I/R group, P1 group, P2 group, P3 group was 0, 2.8±0.4, 2.6±0.5, 2.0±0.7, 1.4±0.5, respectively. The apoptosis rates in S group, I/R group, P1 group, P2 group, P3 group was 6.5%±0.6%, 51.5%±2.8%, 48.2%±0.6%, 24.7%±1.2%, 18.6%±0.8%, respectively. Conclusions Propofol has dose-dependent protection of the brain against I/R injury, and this effect may be involved in the anti-apoptosis effect of propofol.

Key words: Ischemia-reperfusion injury ; Propofol ; Neurological behavior ; Apoptosis;