| Objective: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 were randomly divided into 3 groups,sham-operated group(n=30),ischemia-reperfusion group(control group n=30),atovastatin group(n=30).Each group was divided into 5 subgroups according to reperfusion 0h(n=6),2h(n=6),6h(n=6),24(n=6), 36h(n=6) after ischemia for 2 hours.Atorvastatin(10.0mg/kg/d) was given to atorvastatin group by gastric gavage since the 14th day before ischemia-reperfusion.Sodium chloride solution the same volume to atorvastatin group was given respectively to sham-operated group and ischemia-reperfusion group by gastric gavage since the 14th day,too.Using the improved Longa-Zea method to establish ischemia-reperfusion model in right cerebral middle artery of SD rat, 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% TTC.Judging the ischemic location, measuring the infarction volume with the pathology image analysis system, observing cerebral pathomorphology through HE.Observing the expression of TNF-αand Bax with immunohistological method.Compared respectively:(1)Neurologic impairment score, cerebral infarction volume, cerebral pathomorphology, and the expression of TNF-αand Bax at the same reperfusion time between sham-operated group and control group.(2)Neurologic impairment score, cerebral infarction volume, cerebral pathomorphology, and the expression of TNF-αand Bax at the same reperfusion time between atorvastatin group and control group.(3)Dynamic change of cerebral infarction volume, TNF-αand Bax of infarcted brain tissue at every point of time in control group.(4)Dynamic change of cerebral infarction volume, TNF-αand Bax of infarcted brain tissue at every point of time in atorvastatin group.Results:1.The neurologic impairment score in control group was higer than that in the sham-operated group at every subgroup and the result has remarkable difference(P<0.01);Zea-Longa evaluation have no difference between the atorvastatin group and the control group except in the group of 24h,36h reperfusion following 2h cerebral ischemia(P<0.05).2.Sham-operated group have no infarction area;the infarction volume appear at 2h cerebral ischemia and increased in 24h 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 following 2h cerebral ischemia(P<0.05) and in the group of 36h reperfusion following 2h cerebral ischemia(P<0.01).3.The morphological changes of cerebral tissue stained by HE:Sham-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 betweet tissues and vacuoli-zation. 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 In TNF-a:sham-operated group have a few TNF-αcells; In control group,atorvastatin group, a few TNF-αcells can be seen at 2h cerebral ischemia in the ischemia side of cerebral cortex, Since 2h after reperfusion the expression of TNF-αincreased and reached the peak at 24h after reperfusion.Compared every adjcant reperfusion time point in control group,atorvastatin group, the difference was remarkable(P<0.01). Expect the time of 2h cerebral ischemia, the number of TNF-αcells in control group were higher than that in sham-operated group and the difference was remarkable (P<0.01); Compare with control group, the number of TNF-a cells in atorvastatin group was reduced significantly except 2h cerebral ischemia, P<0.05 at reperfusion 2h,6h,36h, P<0.01 at reperfusion 24h.(2)the expression of Bax:In sham-operated group, double cerebal tissue have a few Bax cells; In control group,atorvastatin group, a few Bax cells can be seen at 2h cerebral ischemia in the ischemia side of hippocampus tissue, Since 2h after reperfusion the expression of Bax increased and reached the peak at 24h after reperfusion.Compared every adjcant reperf-usion time point in control group,atorvastatin group, the difference was remarkable(P< 0.01). Expect the time of 2h cerebral ischemia, the number of Bax cells in control group were higher than that in sham-operated group and the difference was remarkable (P<0.01); Compare with control group, the number of Bax cells in-atorvastatin group was reduced significantly except 2h cerebral ischemia, P<0.05 at reperfusion 2h,6h 36h, P<0.01 at reperfusion 24h.Conclusion:1. TNF-a,Bax may be take part in the process of cerebral ischemia-reperfusion and increased ischemia-reperfusion injury.2.Prevented administration of atorvastatin could decrease focalis chemia-reperfusion injury, relieve the neurological functional defect, reduce infarcted volume, reduce the neuronal degeneration, necrosis and tissue edema, reduce the expression of TNF-aand Bax cells in the ischemia tissue of SD rats.3.Atorvastatin has a neuroprotective effect.The neuroprotective mech-anism of atorvastatin may be related to reducing the expression of TNF-αand Bax.
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