氟西汀预处理对SD大鼠脑缺血再灌注损伤的脑保护作用

Protective effect of fluoxetine pretreatment on focal cerebral ischemia reperfusion damage in SD rat

关键词:  氟西汀  脑缺血再灌注  Caspase-3

Key words:  fluoxetine  ischemia reperfusion  Caspase-3

摘要:

目的　探讨预防性应用氟西汀对SD大鼠局灶性脑缺血再灌注损伤的脑保护作用。　方法　48只健康雄性SD大鼠随机分为脑缺血再灌注组（对照组，n=24）和氟西汀组（n=24），对照组与氟西汀组均制备大鼠右侧大脑中动脉闭塞的脑缺血再灌注模型，分别于术前14 d胃内灌注生理盐水和氟西汀。各组按缺血2 h再灌注2 h、6 h、24 h再分为3个亚组（n=8）。比较相同再灌注时间点两组的神经功能缺损评分、脑梗死体积及缺血侧海马区半胱氨酸蛋白酶-3（Caspase-3）的表达情况。　结果　相同再灌注时间点，氟西汀组较对照组神经功能缺损评分值降低，其中再灌注2 h及6 h，两组间比较差异均无显著性意义（P>0.05），再灌注24 h，两组间比较差异具有显著性意义（P<0.05）；氟西汀组较对照组脑梗死体积减小，其中再灌注2 h及6 h，两组间比较差异均无显著性意义（P>0.05），再灌注24 h，两组间比较差异具有显著性意义（P<0.01）；氟西汀组缺血侧海马区Caspase-3阳性表达细胞数在相同再灌注时间较对照组均减少，差异具有显著性意义（P<0.05）。　结论　氟西汀具有神经保护作用，预防性应用氟西汀在脑缺血再灌注损伤急性期即起显著作用，其机制可能与其减少Caspase-3的表达有关。

Abstract:

Objective To discuss the protective effect of fluoxetine pretreatment on focal cerebral ischemia reperfusion damage in SD rat. Methods Forty-eight healthy male SD rats were established ischemia-reperfusion model in right cerebral middle artery. They were randomly divided into 2 groups, control group and fluoxetine group. 0.9% sodium chloride (10 mL/kg?d) and fluoxetine 0.9% sodium chloride solution (2.0 mg/kg?d) was given respectively to control group and fluoxetine group by gastric gavage at the same time since the 14th day before ischemia-reperfusion.Each group was divided evenly into 3 subgroups according to reperfusion 2 h, 6 h, 24 h after ischemia for 2 h. The neurologic impairment score, cerebral infarction volume, and Caspase-3 expression in the ischemia side of hippocampus tissue were compared between two groups. Results Comparing with control group, the neurologic impairment score and the infarction volume decreased in fluoxetine group at the same time point. There were no significant difference between two groups except in the group of reperfusion 24 h following cerebral ischemia 2 h (P<0.01). The expression of Caspase-3 in the ischemia side of hippocampus tissue decreased at 3 time points of reperfusion in fluoxetine group than that in control group. Conclusion Fluoxetine could have a neuroprotective effect on cerebral ischemia-reperfusion. The protective effect could be related to inhibiting Caspase-3 expression.