| Objective: To evaluate the neuroprotect effect of paroxetine in SD rats following focal cerebral ischemia-reperfusion and its possible mechanism, and the differences of neuroprotect effect between paroxetine and fluoxetine.Methods: 96 healthy male SD rats were randomly divided into 4 groups: sham-operated group,control group,paroxetine group and fluoxetine group, twenty-four rats in each group. Paroxetine solution (2.0mg/kg/d),fluoxetine solution(2.0mg/kg/d) was given respectively to paroxetine group and fluoxetine group by gastric gavage since the 14th day before ischemia-reperfusion. Sodium chloride(10ml/kg/d) was given to both sham-operated group and control group by gastric gavage since the 14th day before ischemia-reperfusion. Except the sham-operated group, others were made ischemia-reperfusion model in right cerebral middle artery of SD rat using the improved Longa-Zea method. Then each group was divided into 4 subgroups according to reperfusion 0h,2h,6h,24h after ischemia for 2h(six rats in each subgroup). Zea-Longa's standards of five grades was used to evaluate the behavioral change ; Tripheny Tetrazalium Chloride (TTC) staining was applied to show cerebral infarction location and measure the infarction volume;Hematoxylin-eosin(HE) staining was used to observe the cerebral pathomorphology and immunohistochemical technique was applied to observe the expression of Caspase-3 and IL-1β.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 had no difference between paroxetine group and control group except in the group of 24h reperfusion;The Zea-Longa evaluation had no difference between paroxetine group and fluoxetine group at any point of reperfusion.2. The infarction volume:Sham-operated group had no infarction area;In control group,paroxetine group and fluoxetine group the infarction volume appeared at 2h cerebral ischemia, increased gradually as the time of the reperfusion went on, reached the peak at 24h after reperfusion in control group while at 6h after reperfusion in paroxetine group and fluoxetine group;The infarction volume had no difference between paroxitinge group and control group except in the group of 24h reperfusion;The infarction volume had no difference between paroxetine group and fluoxetine group at any point of reperfusion.3. The morphological changes of cerebral tissue stained by HE. Sham-operated group had not evident pathological change:In control group the number of neurons in the ischemia side decreased, nerve cells shrinked and degenerated, apparent edema betweet tissues and vacuolization: In paroxeine and fluoxetine group the injured degree of cerebral tissue in the ischemia side lighted compared with the control group, the number of neuron which appeared degeneration and necrosis decreased, vacuolization and intertissue edema became relieve;The morphological changes had no significant difference between the paroxitine group and the fluoxetine group at any point of reperfusion.4. The expression of Caspase-3.In control group,paroxetine group and fluoxetine group, a few of Caspase -3 positive cells can be seen at 2h cerebral ischemia in the ischemia side of hippocampus tissue, 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 ischemi, the difference was remarkable (p﹤0.01): Compare with control group, the number of Caspase-3 positive cells in paroxetine group was reduced significantly except 2h cerebral ischemia, the difference was remarkable(p﹤0.05): The number of Caspase-3 positive cells had no difference between paroxitine group and fluoxetine group at any point of reperfusion.5. Expression of IL-1βIn control group,paroxetine group and fluoxetine group a few of IL-1βpositive cells can be seen at 2h cerebral ischemia in the ischemia side of pallium tissue. increased since 2h after reperfusion and reached the peak at 6h after reperfusion, then it 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 paroxetine group reduced, the difference was remarkable at reperfusion 6h and 24h(p﹤0.05).The number of IL-1βpositive cells had no difference between paroxitine group and fluoxetine group at any point of reperfusion.Conclusions:1. Caspase-3,IL-1βmay be take part in the process of cerebral ischemia-reperfusion and increased ischemia-reperfusion injury.2. Paroxetine have protective effect on brain tissue injury following ischemia-reperfusion. The protective effects may be related to the inhibition of the expression of Caspase-3 and IL-1β.3. The protective effect on brain tissue injury following ischemia- reperfusion have no differences between fluoxetine and paroxetine. |
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