【摘要】 目的研究外源性一氧化碳(CO)对脑缺血-再灌注损伤大鼠海马气体信号分子的影响,探讨脑保护策略.方法 24只Wister大鼠随机分为四组(n=6):对照组(Ⅰ组)、脑缺血-再灌注组(Ⅱ组)、脑缺血-再灌注+低浓度CO组(Ⅲ组)、脑缺血-再灌注+高浓度CO组(Ⅳ组).采用四血管阻断方法制作大鼠全脑缺血-再灌注模型,Ⅰ组行假手术,Ⅲ组和Ⅳ组夹闭两侧颈总动脉前30 min腹腔分别注射CO20 mL/kg或40mL/kg,Ⅰ组和Ⅱ组腹腔注射等量生理盐水.缺血20 min再灌注6 h后处死大鼠取海马,检测大鼠海马组织中H2S、NO和CO的量和CBS、HO和iNOS酶活性变化,以及CBS-mRNA、iNOS-mRNA和HO-1-mRNA表达水平.结果Ⅱ组与Ⅰ组相比大鼠海马中H2S、NO和CO的量增高,CBS、HO和iNOS酶活性增加,CBS-mRNA、iNOS-mRNA和HO-1-mRNA表达增高(P<0.05或P<0.01);Ⅲ组与Ⅱ组比大鼠海马中H2S和CO的量增高,NO的量降低,CBS酶活性增加,iNOS和HO酶活性降低,CBS-mRNA表达增加,iNOS-mRNA和HO-1-mRNA表达降低(P<0.05或P<0.01);Ⅳ组与Ⅱ组相比大鼠海马中H2S和CO的量显著增高,NO的量降低,CBS酶活性增加,iNOS和HO酶活性降低,CBS-mRNA表达增加,iNOS-mRNA和HO-1-mRNA表达降低(P<0.05或P<0.01).结论外源性CO能够诱导脑缺血-再灌注后大鼠海马CBS-mRNA的表达,激活CBS,抑制iNOS-mRNA和HO-1-mRNA的表达,抑制iNOS和HO,对HO-1/CO、CBS/H2S和iNOS/NO系统产生调节作用.更多还原

【Abstract】 Objective To investigate the effect of exogenous carbon monoxide on gaseous signaling molecules in hippocampus of rats with cerebral ischemia-reperfusion injury,and find brain protection methods.Methods 24 Wister male rats aged 3～4 months were randomly even divided into 4 groups:(I)control group,(II)ischemia-reperfusion group,(III)ischemia-reperfusion+20 mL/kg CO group,ischemia-reperfusion+40 mL/kg CO(IV)group.Global cerebral ischemia-reperfusion model was established by 4-vessel occlusion.Rats in group I was carried out sham operation.Rats in Group III and Group IV were respectively intraperitoneally injected 20 mL/kg CO or 40 mL/kg CO before 30 min of clasping bilateral carotid artery.Rats in groupI and group II were injected equation of saline.The carotid clasps were removed after 20 min of 4-vessle occlusion and rats were killed after 6h of reperfusion.The concentration of H2S,NO and CO,the activity of CBS,HO and iNOS,as well as the expression levels of CBS-mRNA,iNOS-mRNA and HO-1-mRNA in hippocampus of rats were measured.Results The concentration of H2S,NO and CO was increased,the activity of CBS,HO and iNOS was increased,CBS-mRNA,iNOS-mRNA and HO-1-mRNA expression was increased in group II as compared with group I(P<0.05 or P<0.01).The concentration of H2S and CO was increased,but NO was decreased,the activity of CBS was increased,iNOS and HO was decreased,iNOS-mRNA and HO-1-mRNA expression was decreased but CBS-mRNA was increased in group III as compared with group II(P<0.05 or P<0.01).The concentration of H2S and CO were significantly increased,but NO were significantly decreased,the activity of CBS was increased,iNOS and HO was decreased,iNOS-mRNA and HO-1-mRNA expression was decreased but CBS-mRNA was increased in group III as compared with group II(P<0.05 or P<0.01).Conclusions Exogenous CO can induce CBS-mRNA expression and inhibit HO-1-mRNA and iNOS-mRNA expression,activiate CBS and inhibit HO and iNOS during global cerebral ischemia-reperfusion in rats.CO can affect HO-1/CO,CBS/ H2S and iNOS/NO systems during global cerebral ischemia-reperfusion in rats.更多还原