异丙酚减轻大鼠脑缺血再灌注损伤

Propofol alleviates cerebral ischemia and reperfusion damage in rats

目的探讨异丙酚对脑缺血再灌注损伤的作用及其可能的机制,为临床用药提供实验依据。方法 将大鼠随机均分为假手术组、异丙酚预处理组、大脑缺血-再灌注组。用Longa法成功制备,左侧大脑中动脉闭塞(MCAO)模型,于再灌注24 h后,取大脑切片行2,3,5-氯化三苯基四氮唑染色,测量并计算脑梗死容积百分比。流式细胞仪检测大鼠脑缺血-再灌注后神经元的凋亡率、坏死率。用Western bolt检测大脑皮质和海马组织中低氧诱导因子-1α(HIF-1α)、半胱氨酸蛋白酶(caspase-3)、凋亡抑制基因(survivn)蛋白表达量。结果 大鼠局灶性脑缺血-再灌注后大脑皮质和海马区出现神经细胞的坏死和凋亡改变,与假手术组相比HIF-1α、caspase-3蛋白表达增加,分别为HIF-1α0.84±0.03、caspase-3 0.57±0.04、假手术组分别为0.46±0.02、0.17±0.01(P<0.05)、survivn蛋白表达减少0.19±0.02,假手术组为0.31±0.01(P<0.05);给予异丙酚预处理后上述变化显著减轻,HIF-1α0.68±0.02、caspase-3 0.29±0.03、survivn 0.52±0.02(P<0.05)。结论 异丙酚可能通过抑制大脑缺氧,抑制神经元的凋亡,从而对大鼠局灶性脑缺血-再灌注损伤发挥保护作用。

Objective To investigate the protective effect of propofol on cerebral ischemia and reperfusion damage in rats.Methods Eighteen adult male SD rats were randomly divided into 3 groups,ischemia group（n=6）,sham injury group（n=6） and propofol group（n=6）.Cerebral ischemia and reperfusion models were made by Longa method,monitoring the rectal temperature and blood sugar.The rats were executed after 24 hours,whose brains were dying by TTC to measure the area of the cerebral infraction.Apoptosis and necrosis rate were detected by cytometry.Western blot was used to detect the expressions of the HIF-1α、caspase-3 and survivn in brain mantle and hippocampi.Results Apoptosis and necrosis appeared in the nerve cells in brain mantle and hippocampi after the cerebral ischemia and reperfusion damage,in the same time,the expressions of HIF-1α and caspase-3 increased and the survivn decreased.However,the apoptosis and necrosis reduced in the propofol groups,and the expression of HIF-1α and caspase-3 were inhibited and the survivn increased.（HIF-1α/α-tublulin ratio 0.68±0.02 vs 0.84±0.03,P0.05,caspase-3/α-tublulin ratio 0.29±0.03 vs 0.57±0.04,P0.05,survivn/α-tublulin ratio0.52±0.02 vs 0.19±0.02,P0.05）.Conclusion Propofol may inhibit hypoxia in the brain and the apoptosis of nerve cells in result of protecting the cerebral ischemia and reperfusion damage in rats.