血红素加氧酶-1对心肺复苏诱发大鼠脑水肿发生的影响

Effect of heme oxygenase-1 on brain edema induced by asphyxial cardiac arrest and resuscitation in rats

目的探讨血红素加氧酶-1（HO-1）对心肺复苏诱发大鼠脑水肿发生的影响。方法雄性SD大鼠40只，随机分为4组（n=10）：假手术组（S组）、心肺复苏组（CAR组）、氯化高铁血红素组（H组）和锡原卟啉组（SnPP组）。CAR组、H组和SnIP组进行窒息性心跳骤停后行心肺复苏，H组预先12h经腹腔注射氯化高铁血红素15mg／kg，SnPP组预先1h经腹腔注射锡原卟啉Ⅸ30μmol／kg。各组于恢复自主循环（ROSC）后1h和6h时断头取脑组织，测定脑皮质、海马和脑干含水量，测定HO．1和水通道蛋白4（AQP4）mRNA表达。结果与s组比较，CAR组和SnPP组皮质和海马含水量增加，海马AQP4mRNA表达上调，H组HO-1mRNA表达上调，SnPP组HO—1 mRNA表达下调（P〈0．05）；与CAR组比较，H组皮质和海马含水量降低，皮质及海马AQP4mRNA表达下调，HO-1mRNA表达上调（P〈0．05），SnPP组T2时皮质及海马AQP4 mRNA表达上调，HO-1mRNA表达下调（P〈0．05），各组脑干含水量比较差异无统计学意义（P〉0．05）。结论HO-1活性增高可减轻大鼠心肺复苏早期脑水肿，其机制可能与下调AQP4的表达有关。

Objective To investigate the effect of heme oxygenase-1 （HO-1） on brain edema in a rat model of asphyxial cardiac arrest and resuscitation. Methods Forty male SD rats weighing 250-300 g were randomly divided into 4 groups （n = 10 each）： group I sham operation; group 11 cardiac arrest （CA）; group m Heroin （HO-1 inducer） and group IV SnPP （HO-1 inhibitor）. Asphyxial eardiae arrest and resuscitation were performed in CA, Heroin and SnPP groups （group II, II, IV ）. Heroin and SnPP groups reeeivod hemin 15 mg/kg intraperitoneally （IP） at 12 h before CA and SnPP IX 30 μmol/kg IP at 1 h before CA respectively, The animals were sacrificed at 1 and 6 h after recovery of spontaneous circulation （ROSC）. The water content of the cortex, hippecampus and brain stem and the expression of HO-1 and aquaporin-4 （AQP4） mRNA in cortex and hippocampus （by RT-PCR） were determined. Results Water content of cortex and hippoeampus was significantly higher at 1 h after ROSC in CA and SnPP groups than in sham operation group and was significantly lower in Hemin group than in CA group. There was no significant difference in water content of brain stem at 1 and 6 h after ROSC among all 4 groups. The expression of AQP4 mRNA was significantly higher in eortex and hippoeampus at 1 h after ROSC in CA and SnPP groups than in sham operation group and was significantly lower in Hemin group than in CA group.Conclusion HO-1 can reduce brain water content at early stage after cardiac arrest and resuscitation by regulating the expression of AQP4.