| Objective:Applying focal ischemia-reperfusion model of SD rat through observing neurologic impairment score,cerebral infarction volume, cerebral pathomorphology and the expression of nuclear factor-KB(NF-κB) and Caspase-3 to discuss whether pretreated with atorvastatin can relieve the injury of local cerebral ischemia-reperfusion in SD rats and possible mechanism.Method:90 healthy male SD rats,3-4 months of age, body weight 200-250g,were randomly divided into 3 groups, sham-operated group(n=30), ischemia-reperfusion group (namely control group,n=30), atorvastatin group(n=30). Each group was divided into 5 subgroups according to reperfusion 0h(n=6),2h(n=6),6h(n=6),24h(n=6),36h(n=6) after ischemia for 2 hours. Sodium chloride solution (lOml/kg/d), Sodium chloride solution (lOml/kg/d) and atorvastatin (10mg/kg/d) was given respectively to sham-operated group, ischemia-reperfusion group and atorvastatin groups once a day by gastric gavage 14 days before ischemia-reperfusion.Using the improved Longa-zea method to establish ischemia-reperfusion model in right cerebral middle artery of SD rat(each group was made ischemia-reperfusion model except the sham-operated group). pull out the string in 2nd hour after ischemia then performing reperfusion. Evaluate the neurologic impairment score by referring to Zea-Longa's standards of five grades. All removed brains were stained respectively with 2% Triphenyl Tetrazalium Chloride(TTC). Judging the ischemic location, measuring the infarction volume with the pathology image analysis system,observing cerebral pathomorphology through Hematoxylin-eosin (HE). Observing the expression of NF-κB and Caspase-3 with immuneo-histochemical technique.Results:1.The neurologic impairment score:At the same point of reperfusion, the neurologic impairment score in control group was increased signi-ficantly compared with sham-operated group and the difference was remarkable(p<0.01); The Zea longa evaluation showed no difference between the atorvastatin group and the control group except in the group of 24h and 36h reperfusion (p<0.05).2.The infarction volume:Sham-operated group had no infarction area;The infarction volume appear at 2h cerebral ischemic and increased in 36h after reperfusion in the control group.The infarction volume appear at 2h cerebral ischemia and increased gradually in the atorvastatin group,and reached the peak at 24h after reperfusion,then it decreased gradually. The infarction volume showed no difference between the atorvastatin group and the control group except in the group of 24h reperfusion(p<0.05) and in the group of 36h reperfusion (P<0.01).3.The morphological changes of cerebral tissue stained by HESham-operated group had no infarction areas and evident pathological change.In control group:the number of neurons at ischemic area decreased, nerve cells shrank and degenerated,apparent edema between tissues and vacuolization. In atorvastatin group:the number of neuron which appeared degeneration and necrosis decreased, vacuolization and inter-tissue edema became relieved compared with control group.4. Immunohistology result:(1) The expression of NF-κB:In control group and atorvastatin group a few of NF-κB positive cells can be seen at 2h cerebral ischemia in the ischemia side of pallium tissue.It increased since 6h after reperfusion and reached the peak at 24h after reperfusion, then decreased gradually. The number of NF-κB positive cells in control group were higher than that in sham-operated group expect the time of 2h cerebral ischemia(p<0.01); Compare with control group,the number of NF-κB positive cells in atorvastatin group reduced,the difference was remarkable at reperfusion 6h(p<0.05),24h and 36h(p<0.01). (2) The expression of Caspase-3:In control group and atorvastatin group a few of Caspase-3 positive cells can be seen at 2h cerebral ischemia in the ischemia side of pallium tissue.It increased since 2h after reperfusion and reached the peak at 24h after reperfusion. The number of Caspase-3 positive cells in control group were higher than that in sham-operated group expect the time of 2h cerebral ischemia(p<0.01);Compare with control group, the number of Caspase-3 positive cells in atorvastatin group reduced, the difference was remarkable at reperfusion 2h,6h(p<0.05),24h and 36h(p<0.01).Conclusion:1.NF-κB, Caspase-3 may be take part in the process of cerebral ischemia-reperfusion injury in inflammation and promote nerve cell apoptosis.2.Prevented administration of atorvastatin could decrease focal ischemia-reperfusion injury,relieve the neurological functional defect, reduce infarction volume,reduce the neuronal degeneration,necrosis and tissue edema,reduce the expression of NF-κB and Caspase-3 in the ischemia tissue in SD rats.3.The protective effect of atorvastatin on cerebral injury induced by ischemia-reperfusion may be related to inhibiting the expression of NF-κB and Caspase-3. Atorvastatin has a significant neuroprotective effect since the acute phase of cerebral ischemia-reperfusion.
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