氟西汀对癫痫合并抑郁大鼠模型海马自噬的作用

目的 探讨氟西汀对癫痫合并抑郁大鼠海马齿状回自噬的影响。方法 将60只SD大鼠随机分为对照组、模型组、氟西汀组、3-甲基腺嘌呤（3-MA）组。采用体重、摄食量、旷场试验评定大鼠抑郁水平；采用免疫组化测定大鼠海马齿状回beclin1、LC3-I、mToR蛋白表达水平，荧光实时定量RT-PCR测定大鼠海马齿状回beclin1、LC3-I、mToR基因表达水平。结果 药物干预后，模型组体重、摄食量、垂直运动次数和水平运动次数明显低于对照组（P<0.01）；氟西汀组、3-MA组经药物治疗后以上指标高于模型组（P<0.01，P<0.05）。模型组海马齿状回beclin1、LC3-I表达显著升高，mToR表达下降，与对照组相比有统计学意义（P<0.01）；氟西汀组、3-MA组大鼠海马齿状回beclin1、LC3-I表达下降，mToR表达升高，与模型组相比差异有统计学意义（P<0.01）。结论 氟西汀可能通过改善癫痫合并抑郁大鼠海马齿状回区beclin1、LC3-I、mToR表达，抑制细胞自噬。

Effect of fluoxetine on autophagy in the hippocampus of rats with epilepsy accompanied by depression

Objective To investigate the effect of fluoxetine on autophagy in the hippocampal dentate gyrus in rats with epilepsy accompanied by depression.Methods A total of 60 Sprague-Dawley rats were randomly divided into control group, model group, fluoxetine group, and 3-methyladenine (3-MA) groups. Body weight, food intake, and open-field test were used to assess the level of depression; immunohistochemistry was used to mesaure the protein expression of beclin1, LC3-I, and mammalian target of rapamycin (mTOR) in the hippocampal dentate gyrus, and quantitative real-time PCR was used to measure the mRNA expression of beclin1, LC3-I, and mTOR.Results After drug intervention, the model group had significantly lower body weight, food intake, and numbers of vertical and horizontal movements than the control group(P<0.01), and the fluoxetine group and the 3-MA group had significantly higher values of the above indices than the model group (P<0.01 or P<0.05). Compared with the control group, the model group had significant increases in the expression of beclin1 and LC3-I and a significant reduction in the expression of mTOR (P<0.01), and compared with the model group, the fluoxetine group and the 3-MA group had significant reductions in the expression of beclin1 and LC3-I and a significant increase in the expression of mTOR (P<0.01).Conclusions Fluoxetine may inhibit autophagy by improving the expression of beclin1, LC3-I, and mTOR in the hippocampal dentate gyrus of rats with epilepsy accompanied by depression.