| Objective: To evaluate the preventive effects and its possible mechanism of fluoxetine on focal ischemia-reperfusion injury in SD rat with hyperglycemia.Methods: 72 healthy male SD rats, with normal blood glucemia(<6mmol/1), were randomly divided into 3 groups: sham-operated group, control group and fluoxetine group, twenty-four rats in each group. Each group was divided into 4 subgroups according to reperfusion 0h(n=6), 2h(n=6), 6h(n=6), 24h(n=6) after ischemia for 2 hours. Sodium chloride solution (10ml/kg/d), Sodium chloride solution(10ml/kg) and fluoxetine (2.0mg/kg) was given respectively to sham-operated group, ischemia- reperfusion group and fluoxetine group by gastric gavage once a day since the 14th day before ischemia-reperfusion. 50% glucose were injected for all animals(3g/kg) by intraperitoneal injection 30 minutes before ischemic operation to establish hyperglycemia model. If blood glucose reached 11.lmmol/l before obstruction, it means model is established successfully. 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).Evaluate the neurological impairment score by referring to Zea-Longa's standards of five grades; All removed brains was stained respectively with 2% Tripheny1 Tetrazalium Chloride(TTC); Judging the ischemic location, measuring the infarction pathomorphology through Hematoxylin-eosin(HE); Observing he expression of IL-1βand Caspase-3 with immunohistochemical technique. Results:1. The neurological impairment score in control group was higher 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 fluoxetine group and the control group except in the group of 24h reperfusion following 2h cerebral ischemia(p<0.05).2. 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 fluoxetine group, and reached the peak at 6h after reperfusion, then it decreased gradually. The infarction volume showed no difference between the fluoxetine group and the control group except in the group of 24h reperfusion following 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 fluoxetine 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 IL-1β: In control group and fluoxetine group a few of IL-1βpositive 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 6h after reperfusion, then decreased gradually. The number of IL-1βpositive 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 IL-1βpositive cells in fluoxetine group reduced, the difference was remarkable at reperfusion 2h,6h(p﹤0.05) and 24h(p﹤0.01).(2) The expression of Caspase-3: In control group and fluoxetine 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 fluoxetine group reduced, the difference was remarkable at reperfusion 2h,6h(p﹤0.05) and 24h(p﹤0.01).Conclusions:1. The expression of IL-1βand Caspase-3 took part in the process of the ischemia-reperfusion and increased ischemia-reperfusion injury in SD rats with hyperglycemia.2. Prevented administration of fluoxetine could decrease focal ischemia-reperfusion injury, relieve the neurological functional defect, reduce infracted volume, reduce the neuronal degeneration, necrosis and tissue edema, reduce the expression of IL-1βand Caspase-3 in the hippocampus tissue in SD rats with hyperglycemia.3. Fluoxetine has a significant protective effect on the cerebral ischemia-reperfusion injury at the state of hyperglycemia. The protective effects of fluoxetine on cerebral injury may be related to the inhibition of the expression of IL-1βand Caspase-3.
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