摘要
目的评价异丙酚对大鼠局灶性脑缺血再灌住损伤时蛋白激酶B（Akt）活性的影响，以探讨异丙酚脑保护作用的机制。方法健康SD大鼠90只，体重260～300g，雌雄不拘，随机分为5组（n=18）：假手术组（S组）；局灶性脑缺血再灌注组（IR组）、P1～3组阻断大脑中动脉2h，开放22h，制备大鼠局灶性脑缺血再灌注模型，分别于再灌注前3min至再灌注5min时经股静脉输注生理盐水2．5ml、异丙酚1、2、5mg／kg（异丙酚采用生理盐水稀释至2．5ml）。于再灌注22h时行神经行为学评分；测定大鼠脑梗死质量、免疫组化法检测大鼠脑组织caspase-3表达、Western blot法检测Akt活性。结果与S组比较，再灌注22h时IR组、P1-3组神经行为学评分、脑梗死质量比升高，脑组织caspase-3表达上调，P1组和P2组Akt活性升高，IR组和P3组Akt活性降低（P〈0．05）；与IR组比较，P1组和P2组大鼠神经行为学评分、脑梗死质量比降低，脑组织caspase-3表达下调，Akt活性升高（P〈0．05）。结论静脉输注异丙酚1、2mg／kg可通过升高Akt活性，抑制脑组织细胞凋亡，减轻大鼠局灶性脑缺血再灌注损伤。
Objective To investigate the effects of different doses of propofol on Akt activity in the brain tissue in rats with fooal cerebral ischemia-reperfusion （FC I/R） injury. Methods Ninety healthy SD rats of both sexes weighing 260-300 g were randomly divided into 5 groups （ n = 18 each） ： group Ⅰ sham operation （S） ; group Ⅱ FC I/R; group Ⅲ, Ⅳ, Ⅴ received iv propofol 1, 2, 5 mg/kg respectively ＋ FC I/R （P1 ,P2 ,P3 ） . FC I/R was produced by 2 h middle cerebral artery occlusion followed by 22 h reperfusion in group Ⅱ - Ⅴ . In group Ⅲ - Ⅴ propofol 1, 2 and 5 mg/kg were injected iv over 8 min starting from 3 min before reperfusion was started. Behavior was assessed using Longa score （0 = no neurological deficit, 4 = unable to crawl） at the end of 22 h reperfusion. Six animals were killed in each group for determination of infarct size, expression of caspase-3 （by immuno- histochemistry） and Akt activity （by Western blot）. Results FC I/R caused cerebral infarct, significantly increased Longa score, and the expression of caspase-3 and decreased Akt activity in the brain tissue. Propofol 1 or 2 mg/kg significantly decreased the infarct size, Longa score and caspase-3 expression and increased phosphorylation of Akt in the brain tissue in group P1 and P2 as compared with group FC I/R （ Ⅱ ）. Conclusion Propofol 1 and 2 mg/kg iv can reduce focal cerebral I/R injury by promoting phosphorylation of Akt in the brain.
出处
《中华麻醉学杂志》
CAS
CSCD
北大核心
2009年第1期60-63,共4页
Chinese Journal of Anesthesiology
基金
天津医科大学科学基金（2006ky39）
