异丙酚对全脑缺血再灌注损伤大鼠的脑保护作用及其机制

背景静脉麻醉药异丙酚可能通过抗凋亡作用保护脑缺血神经元,但是,异丙酚抗凋亡作用的研究还很少,机制尚不明确. 目的观察异丙酚对大鼠全脑缺血再灌注损伤神经元凋亡率、坏死率和凋亡相关基因蛋白表达的影响,探讨异丙酚的脑保护作用及其机制.设计随机对照的实验研究. 地点和对象在首都医科大学附属北京神经外科研究所进行研究.成年雄性Wistar 大鼠 19只,随机分为缺血组( n=7)、异丙酚组( n=7)和假手术对照组(n=5). 干预制备大鼠全脑缺血再灌注模型.异丙酚组再灌注开始后立即静脉输注异丙酚1.5 mL/h,持续 30 min.于再灌注 24 h取脑,用流式细胞仪检测凋亡率,坏死率,bcl-2, Bax和 p53蛋白在大鼠海马神经元中的表达情况. 主要观察指标凋亡率,坏死率,bcl-2, Bax和 p53蛋白在大鼠海马神经元中的表达情况. 结果异丙酚组海马神经元的凋亡率和坏死率[(7.01± 0.79)%和 (12.80± 0.92)% ]较缺血组 [(10.89± 0.80)%和 (16.67± 1.04)% ]明显降低(P< 0.01).异丙酚组 Bax和 p53蛋白表达 [(49.93± 5.41)%和 (10.34± 1.65)% ]较缺血组[(57.05± 1.91)%和 (13.84± 0.97)% ]明显降低 (P分别 < 0.05和 0.01),而异丙酚组bcl 2蛋白表达( 9.45± 1.16)%较缺血组( 9.69± 0.94)%未见显著性差异 (P>0.05). 结论异丙酚能够降低大鼠全脑缺血再灌注神经元的凋亡率和坏死率,起到脑保护作用,其机制可能与降低促凋亡基因Bax和 p53蛋白的表达有关.

Protective effect of propofol on brain in rats with injury of global cerebral ischenia-reperfusion and its mechanism

BACKGROUND:Intravenous anesthetic propofol may protect cerebral ischemic neuron through anti apoptosis.However,research on anti- apoptosis of propofol is very rare,and its mechanism is also not definite. OBJECTIVE:To observe the effect of propofol on apoptosis and necrosis rates of neuron in rats with injury of global cerebral ischemic reperfusion and the expression of genetic protein related to apoptosis and explore the protective effects of propofol on brain and its mechanism. DESIGN:A randomized and controlled experimental study. SETTING and MATERIALS:The research was done in Beijing Neurosurgical Institute affiliated to the Capital University of Medical Sciences.Nineteen male adult Wistar rats were randomly divided into ischemic group(n=7),propofol group(n=7) and sham operation group(n=5). INTERVENTIONS:Rat models of global cerebral ischemia reperfusion were eatablished.1.5 mL/hour propofol was given intravenously right after reperfusion began in propofol group,persisting 30 minutes.Brain was taken out at the time point of 24 hours of reperfusion.Apoptosis and necrosis rate and protein expression of bcl-2, Bax and p53 in hippocampal neuron of rats were detected by flow cytometry. MAIN OUTCOME MEASURES:Apoptosis rate, necrosis rate and protein expression of bcl-2, Bax and p53 in hippocampal neuron of rats. RESULTS:Apoptosis and necrosis rate[(7.01± 0.79)% and(12.80 ± 0.92)% ]of hippocampal neuron in propofol group decreased significantly (P< 0.01), as compared with ischemic group[(10.89± 0.80)% and(16.67± 1.04)% ].Bax and p53 protein expression in propofol group[(49.93± 5.41)% and (10.34± 1.65)% ] decreased significantly(P < 0.05 and P< 0.01,respectively),as compared with ischemic group[(57.05± 1.91)% and(13.84± 0.97)% ], while,bcl-2 protein expression in propofol group [( 9.45± 1.16)% ] had no significant difference from that in ischemic group[( 9.69± 0.94)% ](P >0.05). CONCLUSION:Propofol can decrease apoptosis and necrosis rates of neuron in rats with global cerebral ischemic reperfusion so as to protect the brain.The mechanism may have some relationships with decreasing the protein expression of Bax and p53,the genes promoting apoptosis.