异丙酚对脑缺血再灌注损伤大鼠海马组织细胞间粘附分子-1及核转录因子-κB表达的影响

Effects of propofol on the expression of intercellulor adhesion molecule-1 and NF-κB in hippocampus following global cerebral ischemia-reperfusion in rats

目的观察异丙酚对大鼠脑缺血再灌注损伤后海马组织细胞问粘附分子-1(ICAM-1)及核转录因子-κB(NF-κB)基因表达的影响,探讨异丙酚脑保护作用的机制。方法雄性Wistar大鼠40只,随机分为假手术组(A组)、缺血再灌注对照组(B组)和缺血再灌注异丙酚预处理组(C组),按异丙酚用量又分为50mg·kg-1、100mg·kg-1和150mg·kg-1三个亚组,缺血前10min腹腔注射。全脑缺血10min再灌注24h时,断头处死大鼠。用逆转录-聚合酶链反应技术检测海马组织ICAM-1与NF-κBmRNA的表达,用免疫组织化学方法检测海马组织ICAM-1及NF-κB蛋白的表达,用电镜检测海马组织超微结构的改变。结果脑缺血再灌注后海马组织ICAM-1与NF-κBmRNA的表达水平增高,异丙酚可下调ICAM-1与NF-κBmRNA的表达;缺血再灌注亦可明显诱导ICAM-1与NF-κB蛋白在海马的表达,异丙酚预处理可显著抑制ICAM-1与NF-κB蛋自在海马的表达;缺血再灌注后海马线粒体超微结构发生明显损害,异丙酚可减轻海马线粒体的损伤程度。结论异丙酚可能通过抑制:ICAM-1与NF-κB基因的表达而对脑缺血再灌注损伤起一定的保护作用。

Objective To investigate the effects of propofoi on the expression of intercellular adhesion molecule-1 (ICAM-1) and nuclear transcription factor-kappa B(NF-κB) protein and mRNA in hippocampus following global cerebral ischemia-reperfusion (I/R) in rats.Methods Forty male Wistar rats weighing 250-300 g were randomly divided into 3 groups: group A sham-operated ( n = 8) ; group B I/R (n = 8) and group C propofoi + I/R ( n = 24). Group C was further divided into 3 subgroups ( n = 8 in each subgroup) according to the doses of intraperitoneal propofoi given 10 min before global cerebral I/R (C1 50 mg· kg-1 ; C2 100 mg·kg-1 ; C3 150 mg·kg-1 ). Global cerebral I/R was produced by 4-vessel occlusion method. Bilateral carotid arteries were released for reperfusion after 10 mm cerebral ischemia. The animals were decapitated at the end of 24 h reperfusion and the brains were removed. The levels of ICAM-1 and NF-κB mRNA expression in the hippocampus were detected by using semi-quantitative RT-PCR technique. The expression of ICAM-1 and NF-κB protein in the brain was determined by immuno-histochemical method. The nritochondrial ultrastructure was examined by electron microscopy. Results I/R induced significant increase in the expression of ICAM-1 and NF-κB protein and mRNA in group B as compared to group A. Intraperitoneal propofoi pretreatment significantly inhibited the increase in ICAM-1 and NF-κB protein and mRNA expression induced by global cerebral I/R. The levels of ICAM-1 and NF-κB expression were significantly higher in subgroup Cl than in subgroup C2 and C3 ( P < 0.05), but the difference between subgroup C2 and C3 was not significant ( P > 0.05). Electron microscopic examination showed that there were severe mitochondnal edema and degeneration in I/R group (group B) and the damage was mild in the propofoi pre-treated group.Conclusion Global cerebral I/R induces significant increase in the expression of ICAM-1 and NF-κB Propofoi pretreatment can significantly inhibit I/R-induced increase in ICAM-1 and NF-κB expression.