| 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(n=30): sham-operated group, control group and atorvastatin group. Each group was divided into 5 subgroups according to reperfusion 0h(n=6), 2h(n=6), 6h(n=6) , 12h(n=6), 24h(n=6) after ischemia for 2 hours. Sodium chloride solution (10ml/kg/d), sodium chloride solution (10ml/kg/d), sodium chloride solution (10ml/kg/d) and atorvastatin (10.0mg/kg/d) suspension were given respectively to 3 groups above by gastric gavage once a day since the 14th day before ischemia-reperfusion.The sham-operated group:sewing up the skin after exposing the common carotid artery(CCA) in the right side. The control group and the atorvastatin pretreatment group: 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% Tripheny1 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 Il-1βand Bcl-2 with immunohistochemical technique.Results:1. The neurologic impairment score in the control group was higher than that in the sham-operated group at every subgroup and the result has noticeable difference (p﹤0.01); Zea longa evaluation showed no difference between the atorvastatin group and the control group except in the groups of 12h and 24h reperfusion following 2h cerebral ischemia (p﹤0.05).2. The sham-operated group bilateral brain tissue, the control group and the atorvastatin group non-ischemic side of brain tissue had no infarction areas. In the control group,the infarction volume appeared in the ischemic side at 2h after cerebral ischemia and increased gradually as the time of the reperfusion went on in 24 hours. In the atorvastatin group,the infarction volume appeared in the ischemic side at 2h after cerebral ischemia and increased as the time of the reperfusion went on, reaching the peak at 6h, then decreased gradually, but the infarction volume at 24h after reperfusion was still higher than that at 2h after reperfusion. In the control group and the atorvastatin group,the difference in each group of the adjacent reperfusion time point was significant(p﹤0.01).The infarction volume showed no difference between the atorvastatin group and the control group except in the group of 12h reperfusion following 2h cerebral ischemia (p﹤0.05) and in the group of 24h reperfusion follow- ing 2h cerebral ischemia (p﹤0.01)3. Morphology of cerebral tissue stained by HESham-operated group had no infarction areas and evident pathological changes. 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) Comparison between the control group and the sham-operated group at the same point of reperfusion time: The expression of IL-1βand Bcl-2 in the ischemia side of hippocampus tissue increased obviously (p﹤0.01) except at 2h cerebral ischemia.(2) Comparison between the atorvastatin group and the control group at the same point of reperfusion time: The expression of IL-1βin the ischemia side of hippocampus tissue decreased, p﹤0.05 at referfusion 6h, p﹤0.01 at reperfusion 12h and 24h. The expression of Bcl-2 in the ischemia side of hippocampus tissue increased, p﹤0.01 at reperfusion 12h and 24h.There was no difference between the atorvastatin group and the control group at the other referfusion time.(3) Dynamic change of expression of IL-1βand Bcl-2 in the control group: There were a few of IL-1βpositive cells in the ischemia side of hippocampus tissue at 2h cerebral ischemia. The expression increased since 2h after reperfusion and reached the peak at 6h after reperfusion, then it decreased gradually, there was significant difference among each point of time (p﹤0.01). There were few of Bcl-2 positive cells in the ischemia side of hippocampus tissue at 2h cerebral ischemia. The expression increased since 2h after reperfusion and reached the peak at 12h after reperfusion, then it decreased gradually, there was significant difference among each point of time (p﹤0.01).(4) Dynamic change of expression of IL-1βand Bcl-2 in the atorvastatin group: There were a few of IL-1βpositive cells in the ischemia side of hippocampus tissue at 2h cerebral ischemia. The expression increased since 2h after reperfusion and reached the peak at 6h after reperfusion, then it decreased gradually, there was significant difference among each point of time (p﹤0.01). There were few of Bcl-2 positive cells in the ischemia side of hippocampus tissue at 2h cerebral ischemia. The expression increased since 2h after reperfusion and reached the peak at 12h after reperfusion, then it decreased gradually, there was significant difference among each point of time (p﹤0.01).Conclusions:1. From the above, we can see that the expression of IL-1βand Bcl-2 take part in the process of the ischemia-reperfusion, the former enable the injury aggravated,and the later so that mitigate damage.2. Prophylactic use of atorvastatin could decrease the focal ischemia-reperfusion damage, relieve the neurological functional defect, reduce the infarct volume, reduce the neuronal degeneration, necrosis and tissue edema, reduce the expression of IL-1βand increase the expression of Bcl-2 in the ischemia side of hippocampus tissue in SD rats.3. Atorvastatin has a neuroprotective effect. Preventive applications atorvastatin can reduce the cerebral ischemia-reperfusion injury. The neuroprotective mechanism of atorvastatin may be ralated to reducing the expression of IL-1βand increasing the expression of Bcl-2.
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