外源性一氧化氮对脑缺血-再灌注损伤大鼠海马气体信号分子的影响

Effects of exogenous nitric oxide on hippocampus gaseous transmitters in rats with global cerebral ischemic-reperfusion injury

目的研究外源性一氧化氮(NO)对脑缺血-再灌注(I-R)损伤大鼠海马气体信号分子的影响。方法 24只Wistar大鼠随机均分为四组:脑I-R对照组(Ⅰ组),脑I-R+低浓度硝普钠(SNP)组(Ⅱ组)和脑I-R+高浓度SNP组(Ⅲ组),对照组(Ⅳ组)。夹闭两侧颈总动脉制作大鼠全脑I-R模型。颈总动脉夹闭前30min分别腹腔注射SNP2mg/kg(Ⅱ组)或4mg/kg(Ⅲ组)。脑缺血20min,再灌注6h后处死大鼠,取脑海马组织,检测硫化氢(H2S)、NO和CO的量和胱硫醚β-合酶(CBS)、血红素氧合酶-1(HO-1)和诱导型一氧化氮合酶(iNOS)活性,以及CBS mRNA、iNOS mRNA和HO-1-mRNA表达水平。结果Ⅰ、Ⅱ、Ⅲ组大鼠海马中H2S、NO和CO的含量和CBS、HO和iNOS的活性均高于Ⅳ组;CBSmRNA、iNOS mRNA和HO-1 mRNA表达增高(P<0.05或P<0.01);Ⅱ、Ⅲ组大鼠海马中的上述指标均高于Ⅰ组(P<0.05或P<0.01)。结论外源性NO能诱导脑I-R后大鼠海马CBS mRNA和HO-1 mRNA表达,激活CBS和HO。在脑I-R损伤过程中存在NO对CBS/H2S和HO-1/CO系统的调节。

Objective To investigate the effects of exogenous nitric oxide（NO） on gaseous transmitter molecule of the hippocampus in rats with global cerebral ischemic-reperfusion（I-R） injury.Methods Twenty-four Wistar male rates were randomly divided into 4 groups of sham operation（group S）,I-R control（group I-R）,I-R plus sodium nitroproside（SNP） 2 mg/kg（LSNP） or plus SNP 4 mg/kg（group HSNP） with 6 rats each.Global cerebral I-R model was established by 4-vessel occlusion.SNP was injected at 30 min before clamping the bilateral carotid arteries in groups of LSNP and HSNP.The carotid arteries were clasped for 20 min.The rats were killed after cerebral reperfusion for 6 h.The concentrations of hydrogen sulfide（H2S）,NO and CO,the activity of cystathionine beta synthase（CBS）,HO and inducible nitric oxide synthase（iNOS）,as well as the expression levels of CBS mRNA,iNOS mRNA and hemeoxygenase-1（HO-1） mRNA in the hippocampus were measured.Results Compared to group S,the concentrations of H2S,NO and CO,the activities of CBS,HO and iNOS and the expressions of CBS mRNA,iNOS mRNA and HO-1 mRNA in group I-R were increased（P〈0.05 or P〈0.01）,which were all higher in groups of LSNP and HSNP than those in group I-R（P〈0.05 or P〈0.01）.Conclusion Exogenous NO can induce the expressions of CBS mRNA and HO-1 mRNA,activate CBS and HO in rats with global cerebral I-R injury,indicating that NO has a modulation effect on the CBS/ H2S and iNOS/NO systemes.