Effects Of Aspirin Preconditioning On NO Content, Expression Of INOS And NF-κB In Rats Focal Cerebral Ischemia Reperfusion

Objective: To investigate the effects of aspirin preconditioning on nitrogen monoxidum(NO), expression of induciable nitricoxide synthase(iNOS) and nuclear factor-kappa B(NF-κB) in rats focal cerebral ischemia reperfusion. To explore protective effects of aspirin on the neurons and the optimal dosage.Methods: Established the rat middle celebral artery (MCA) cerebral ischemia/reperfusion(CI/RP) model with suture occlusion technique according to classic Zea Longa method and then the rats were randomly devided into six groups: normal control group(n=12), sham-operation group (n=12), ischemia group(n=12) and three aspirin preconditioning groups(n=36) with different dose of ASA(low dose: 10mg/kg; middel dose: 50mg/kg and large dose:150mg/kg) via a lavage rote right for five days before focal cerebral ischemia. The middle celebral artery occlusion model was made by the suture method at the sixth day. After consciousness, the neurologic impairment evaluation scores were record on Longa 5-point scale. The rats were then killed at the seventh day and the blood from abdominal aorta of rats was prepared for the measurement of NO. Some of the brains were removed to measure the infarct volume by TTC staining and the others were detected expression of iNOS and NF-κB by immunohistochemistry technology.Results: 1.Rats had neurologic impairment in various degree appeared in the ischemia group and aspirin preconditioning groups after CI/RP. Compared with the ischemia group, the neurological scores of the aspirin preconditioning groups reduced obviously, the effects of low and middle dose groups showed an evident superiority(p<0.01), the effects of large dose group showed an superiority(p<0.05). There was no significant difference among aspirin preconditioning groups (p>0.05). 2.Compared with normal control group and sham-operation group, the NO contents of the blood were increased obviously in the ischemia group(p<0.01). Compared with the ischemia group, the NO contents of the aspirin preconditioning groups degraded obviously, the effects of low,middle and large dose groups showed an evident superiority (p<0.01). Among aspirin preconditioning groups, middle dose group and large dose group had no difference(p>0.05), there had some differences between with low and middle dose group, between with low and large dose group(p<0.05). 3.The infarct area, where showed white colour because not stained by TTC, can be distinguished clearly to the normal brain where showed red colour. Compared with the ischemia group, the infarct volume of the aspirin preconditioning groups reduced obviously, the effects of low and middle dose groups showed an evident superiority(p<0.01), the effects of large dose group showed an superiority (p<0.05). Among aspirin preconditioning groups, low dose group and middle dose group had no difference(p>0.05), there had some differences between with low and large dose group, between with middle and large dose group(p<0.05). 4. Immunohistochemistry technology: Compared with normal control group and sham-operation group, the expression of iNOS and NF-κB were increased obviously in the ischemia group(p<0.01). Compared with the ischemia group, the expression of iNOS and NF-κB of the aspirin preconditioning groups reduced obviously, the effects of low and middle dose groups showed an evident superiority (p<0.01), the effects of large dose group showed an superiority (p<0.05). Among aspirin preconditioning groups, low dose group and middle dose group had no difference (p>0.05), but there had some differences between with low and large dose group, between with middle and large dose group (p<0.05).Conclusion: 1.The application of aspirin preconditioning can decrease neurological scores and hastene recovery of limbs after CI/RP; 2.The effects of aspirin preconditioning can reduce infarct volume after CI/RP; 3.The application of aspirin preconditioning after CI/RP can inhibit the expression of iNOS,reduce NO contents and inhibit the activation of NF-κB,which might be mechanism of aspirin achieve neuroprotections; 4.The effect of low and middle dose of aspirin show an superiority to the large dose, which means that the neuroprotection of aspirin does not present an increasing level as the dose of aspirin adding.