Interactions between endogenous carbon monoxide and nitric oxide during rat global cerebral ischemic-reperfusion injury

Objective To investigate the interaction between HO-1/CO and iNOS/NO systems during global cerebral ischemia-reperfusion(IR) injury and retrieval brain protection methods.Methods Twenty-four Wistar male rates aged 3-4 months were equally randomized into 4 groups: control(C) group,IR group,IR +aminoguani-dine(A)group,IR +zinc-protoporphyrin(Z)group.Global cerebral IR was established by 4-vessel occlusion.Group C was carried out sham operation.Group A and Group Z rats were respectively intraperitoneal injected 500 mg/kg aminoguanidine or 45 μmol/kg zinc protoporphyrin before 30 min of clasping bilateral carotid artery,group C and group IR were injected equation saline.The carotid clasps were removed after 20 min of 4-vessle occlusion and rates were killed after 6 h of reperfusion.The concentration of CO,NO,MDA,the activity of SOD,and expression of HO-1-mRNA and iNOS-mRNA in rats' hippocampus were measured.The mitochondrial structure was observed by electronmicroscope.Results The concentration of NO,CO and MDA was significantly increased,SOD was significantly decreased,iNOS-mRNA and HO-1-mRNA expression has increased in group IR as compared with group C(P0.01).Meanwhile the structure of mitochondrial has destroyed.Group A level of NO and MDA were decreased,but SOD were increased,iNOS-mRNA expression was decreased compared with group IR(P0.01),mitochondrial destroying has mitigated.Group Z CO and SOD were significantly decreased,but level of NO and MDA were increased,HO-1-mRNA was decreased as compared with group IR(P0.01),mitochondrial destroying has aggravated.Conclusion iNOS/NO system can induce nerve cells damage,but HO-1/CO plays an against-damage role in cerebral ischemia-reperfusion.Inhibitor of iNOS has possessed neuroprotective effects.