一氧化氮在异氟烷预处理脑保护中的作用

Effect of nitric oxide on isoflurane preconditioning against brain ischemia-reperfusion

目的明确一氧化氮在异氟烷预处理脑保护中的作用。方法75只雄性沙士鼠,随机分5组。假手术组(SHAM组):只分离双侧颈总动脉而未予夹闭;缺血再灌注组(I/R组):夹闭双侧颈总动脉5min后开放造成I/R;异氟烷预处理组(ISO组):I/R前60min吸入1.2%～1.5% ISO 30min;AG+ISO组:腹腔内注射AG200mg/kg,30min后同ISO组;氨基呱组(AG组):I/R前30min注射AG。再灌注24h,取鼠前脑,观察线粒体超微结构、线粒体游离Ca2+浓度和MPTP开放程度。结果在I/R组和AG组,线粒体明显肿胀、Ca2+浓度增加及MPTP大量开放,AG+ISO组,部分线粒体未见明显损伤,部分线粒体损伤较明显;Ca2+浓度高于SHAM组和ISO组,而MPTP的开放明显高于ISO组(P<0.05)。结论一氧化氮参与了异氟烷预处理对沙士鼠脑I/R损伤保护作用的信号传导。

[Objective] To investigate the effect of nitric oxide（NO） on isoflurane （ISO） preconditioning against brain ischemia-repeffusion（I/R）. [Methods] Seventy-five male gerbils were randomly divided into 5 groups （n =15）： group SHAM; group I/R; group ISO; group AG＋ISO and group AG. Global cerebral I/R was produced by occlusion of bilateral common carotid arteries for 5 min and confirmed by isoelectric potential on EEG. In group ISO the animals inhaled 1.2%-1.5% isoflurane for 30 min followed by 30 min wash-out period before I/R. In group AG＋ISO, 30 mln after AG 200 mg/kg i.p. isoflurane was inhaled as group ISO ,and AG was injected 30 min before I/R in group AG. The animals were killed 24 h after global cerebral ischemia and their forebralns were excised for electron microscopic examination of mltochondria, measurement of mitochondrial permeability transition pore （MPTP） and calcium content in mitochondria. [Results] Marked swelling of mitochondria with disrupted cristae and higher Ca^2＋ concentration and more open MPTP were observed in group I/R and group AG, while in group SHAM relative intact mitochondria and lower Ca^2＋ concentration and MPTP were seen. In group AG＋ISO, the mitochondria was injuried between group I/R and group SHAM, the Ca^2＋ concentration was higher and MPTP more open than those in group SHAM and ISO （P 〈0.05）. [Conclusion] NO is involved in the signaling pathway of isoflurane preconditioning induced protection effect on gerbil brain against I/R.