丙泊酚对全脑缺血／再灌注损伤大鼠保护作用研究

The protective effect of propofol against global cerebral ischemiaJreperfusion injury in rats

目的探讨丙泊酚对大鼠全脑缺血／再灌注损伤（ischemia／reperfusion injury，I／RI）的保护作用。方法65只Wistar雄性大鼠采用完全随机法分为5组：假手术组（S组）、缺血，再灌注（ischemia／reperfusion，I／R）组（I／R）组、丙泊酚组1（P1）、丙泊酚组2（P2）、丙泊酚组3（P3），每组13只。采用双侧颈总动脉夹闭＋全身低血压[平均动脉压（MAP）控制在35mmHg～45mmHg（1mmHg=0．133kPa）]法制备全脑I／RI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组在全脑缺血前分别泵入丙泊酚0．5、1．0、1．5mg·kg-1．min-1，维持1h。每组随机选8只大鼠分别再灌注后6、24、48、72h、4、5、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（每组5只）。25只Wistar雄性大鼠（每组5只）于1／R24h后应用流式细胞仪检测全脑细胞凋亡情况。结果I／R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组差异无统计学意义外，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组、I／R组、P1组、P2组、P3组分别为0，2．8±0．4，2．6±0．5，2．0±0．7，1．4±0．5；异丙酚预处理组P2、P3能明显减轻全脑I／R后组织病理学改变；应用流式细胞仪检测神经细胞凋亡，5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I／RI的保护作用与剂量相关，可能与丙泊酚的抗凋亡作用有关。

Objective To investigate the protective effects of propofol on global cerebral ischemia-reperfusion injury （I/RI） in rats and the underlying mechanism. Methods 65 male Wistar rats weighting 250 g-300 g were randomly divided into 5 groups （n=13）： group S sham operation, group ischemia/reperfusion （I/R）, group PI propofol （0.5 mg·kg-1·min-1）±I/R, group P2 propofol （1.0 mg·kg-1·min-1）±I/R and group P3 propofol （1.5 mg ·kg-1·min-1 ）±I/R. I/R group was induced by occlusion of bilateral common carotid arteries combined with controlled hypotension for 10 min. In group P1, P2and P3, propofol was continued intravenous infusion for 60 min before I/R. The neurological behavior was evaluated at 6, 24, 48, 72 h, 4, 5, 6 d and 7 d after I/R. Rats were killed at 7 d 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 24 h of reperfusion in each group. Results The rats subjected to ischemic and reperfusion appeared behavioral defects. The behavior of animals was significantly better in group P2 and in groups P3 than that of in groups PI and 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, P3group was （6.5±0.6）, （51.5±2.8）, （48.2±0.6）, （24.7±1.2）, （18.6±0.8）%, respectively. Conclusion Propofol confers dose-dependent protection against cerebral I/R injury, and this effect may be involved in the anti-apoptosis effect of propofol.