丙泊酚在正颌外科控制性降压中的脑保护作用机理

Cerebral protective mechanism for propofol in controlled hypotension in orthognathic surgery

目的:通过大鼠实验,研究丙泊酚在大鼠脑缺血再灌注损伤时对线粒体通透性转换孔活性的影响程度,及其抑制神经细胞凋亡坏死的作用机制。以探讨其在正颌外科控制性降压中的脑保护作用机理。方法:选取健康雄性大鼠30只,体重250～300g,采用"双侧颈总动脉阻断法"建立前脑缺血再灌注模型,左侧侧脑室于假手术组(C组)、缺血再灌注组(I/R)组注射生理盐水1ml/kg,丙泊酚干预组(P组)射注丙泊酚1mg/kg,24h后断头提取海马组织线粒体,加入CaCl2于37℃下形成钙超载后孵育5min。电镜观察其微观组织形态学改变,采用紫外分光光度计法来观察线粒体通透性转换孔开放程度。结果:电镜下C组线粒体结构完整,排列密集;I/R组可见线粒体明显肿胀、嵴断裂、膜破裂;P组可见线粒体部分肿胀,嵴部分断裂,但损伤程度轻于I/R组。与C组相比较,I/R组和P组线粒体吸光度值明显下降(P<0.05);与I/R相比,P吸光度值下降幅度减小(P<0.05)。丙泊酚组细胞肿胀坏死明显减轻,凋亡细胞及坏死细胞明显减少。结论:丙泊酚能够改善大鼠前脑缺血再灌注后线粒体形态,其机制可能与其抑制线粒体通透性转换孔(MPTP)开放有关,从而改善线粒体功能,抑制神经细胞凋亡坏死,减轻脑缺血再灌注损伤。这说明丙泊酚在正颌外科控制性降压中使用时对大脑有良好的保护作用,可以大幅度提高手术安全效果,具有重要的临床指导意义。

Objective To investigate the effect of propofol on rat forebrain ischemia reperfusion induced mitochondrial damage. Methods 30 male rats weighing 250g-300g were randomly divided into three groups （n=10）：control group （C）; ischemia reperfusion group （I/R）; propofol group（P）. Forebrain cerebral ischemia reperfusion was produced by 2-vessel occlusion method. Bilateral carotid arteries were released after 10 minutes cerebral ischemia. Normal saline 1 ml/kg and propofol 1 mg/kg were separately injected into the lateral cerebral ventricle by micro syringe in group I/R and group P. The animals were decapitated at the end of the 24h reperfusion and the hippocampal were separated.The mitochondria of hippocampal in each group were isolated. The mitochondria of three groups were incubated by CaCl2 for 5 mins at 37%. Morphological changes of mitochondria were observed by using electron microscopy. Mitochondrial permeability transition pore （MPTP） opening were detected by ultravioletvisible absorption spectroscopy （n=10）. ResuLts Group C showed normal mitochondrial ultrastructure; Significant mitochondrial swelling, cristae disrupted and membrane rupture were showed in group I/R; Morphological changes of mitochondria in group P were between group C and group I/R. Absorbance values of mitochondrial decreased in group C, I/R and P. Compared with group C, absorbance values of mitochondrial were lower in group I/R and P （P〈0.05）.The decrease of absorbance values of mitochondria was reduced in group I/R compared with that in group P （P〈O.05）. Conclusion Propofol shows better improvement of mitochondrial function induced by calcium overload after forebrain ischemia reperfusion, indicated by inhibition of MPTP opening. This may be involved in the mechanisms of brain protection of propofol and can use in clinical.