氟西汀对癫痫合并抑郁大鼠海马GFAP、NeuN表达的影响

目的探讨氟西汀对癫痫合并抑郁大鼠海马齿状回胶质纤维酸性蛋白(GFAP)、神经元核抗原(NeuN)表达的影响。方法SPF级SD大鼠60只,随机分为对照组、模型组、氟西汀低、中、高剂量组各12只。模型组和对照组给予等剂量生理盐水,1次/d,腹腔注射;氟西汀低、中、高剂量组给予氟西汀(5.0、7.5、10.0 mg/kg),1次/d,腹腔注射。治疗28 d,采用强迫游泳实验和旷场实验测试大鼠行为学表现,采用免疫组化、RT-PCR检测海马GFAP、NeuN表达。结果造模后,与对照组相比,模型组、氟西汀低、中、高剂量组不动时间延长,垂直运动次数、水平运动次数明显下降(P<0.05)。干预后,模型组不动时间明显长于对照组,垂直运动次数、水平运动次数明显低于对照组(P<0.01);与模型组相比,氟西汀低、中、高剂量组不动时间缩短,垂直运动次数、水平运动次数明显增加(P<0.05);尤其是氟西汀高剂量组,较氟西汀低、中剂量组相比有统计学意义(P<0.05)。免疫组化、RT-PCR显示,与对照组相比,模型组GFAP表达明显增加、NeuN表达明显下降(P<0.05);与模型组相比,氟西汀低、中、高剂量组GFAP表达明显下降、NeuN表达明显增加(P<0.05);尤其是氟西汀高剂量组,较氟西汀低、中剂量组相比有统计学意义(P<0.05)。结论氟西汀可能通过改变海马区GFAP、NeuN表达,并呈剂量依赖性,发挥神经保护作用,改善癫痫合并抑郁大鼠抑郁症状。

Effect of fluoxetine on GFAP,NeuN in hippocampus of epileptic rats with depression

Objective To explore the effect of fluoxetine on the expression of glial fibrillary acidic(GFAP)protein,neuron specific nuclear(NeuN)protein in hippocampal dentate gyrus of epileptic rats with depression.Methods Totally 60 SPF SD rats were divided into 5 groups randomly:control,model,fluoxetine low/medium/high dose groups(n=12).The fluoxetine low/medium/high dose groups were given corresponding concentration of fluoxetine(5.0,7.5,10.0 mg/kg respectively,once a day,i.p.),while the model and the control groups received an equal dose of normal saline(once a day,i.p.).After 28 d treatment,the behavior changes were assessed by using the forced swimming and open-field tests.The expressions of GFAP and NeuN in hippocampal dentate gyrus were measured with immunohistochemistry and RT-PCR.Results After modeling,compared with the control group,duration of immobility were significantly extend,scores of vertical and horizontal movement decreased significantly in the model,fluoxetine low/medium/high dose groups(P<0.05).After treatment,duration of immobility in the model group was longer,but scores of vertical and horizontal movement were significantly lower than those in the control group(P<0.05).Compared with the model group,duration of immobility shorten significantly,scores of vertical and horizontal movement were significantly higher in the fluoxetine low/medium/high dose groups(P<0.05),especially in the fluoxetine high dose group.Compared with the control group,expression of GFAP increased significantly,while the NeuN decreased significantly in the model group(P<0.05).Compared with the model group,expression of GFAP decreased,while the NeuN increased significantly in the fluoxetine low/medium/high dose groups(P<0.05),especially in the fluoxetine high dose group.Conclusions Fluoxetine exerts neuroprotective effect and improves depressive symptoms on epileptic rats with depression in a dose-dependent manner by changing the expressions of GFAP,NeuN in the hippocampus.