艾司西酞普兰对抑郁模型大鼠海马胶质细胞源性神经营养因子及细胞凋亡相关因子表达的影响

Effects of escitalopram on the expression of glial cell line.derived neurotrophic factor and apoptosis related factors in hippocampus of depression model rats

目的 探讨艾司西酞普兰对抑郁模型大鼠海马胶质细胞源性神经营养因子（GDNF）及细胞凋亡相关因子表达的影响.方法 雄性SD大鼠按随机数字表分为对照组（A）、对照加药组（B）、抑郁组（C）和抑郁加药组（D）,以慢性轻度不可预见性的应激结合孤养建立抑郁动物模型,应激同时B、D组予艾司西酞普兰（10 mg/kg）干预,A、C组予等体积生理盐水灌胃处理,共28 d.TUNEL法检测海马细胞凋亡情况,用实时荧光PCR方法检测海马GDNF、Bax、Bcl-2、Caspase3 mRNA的表达.结果 ①与A组[（12.0±1.83）个]比,C组[（19.3±1.77）个]海马细胞凋亡数显著增加（P＜0.01）,而B组[（11.9±1.91）个]细胞凋亡数无明显差异（P＞0.05）；与C组比,D组[（12.7±1.77）个]细胞凋亡数显著减少（P＜0.01）.②与A组比,C组海马GDNF、Bcl-2 mRNA表达减少（P＜0.01）,Bax、Caspase3 mRNA表达增加（P＜0.01）；与C组比,D组GDNF、Bcl-2 mRNA表达增加（P＜0.01）,Bax、Caspase3 mRNA表达降低（P＜0.01）.结论 艾司西酞普兰可改善抑郁大鼠的抑郁行为及预防海马细胞凋亡,其机制可能是通过增加海马GDNF mRNA的表达,上调Bcl-2及下调Bax、Caspase3 mRNA的表达有关.

Objective To explore the effects and mechanisms of escitalopram on the expression of glial cell line-derived neurotrophic factor（GDNF） in hippocampus of depression model rats.Methods 40 male SD rats were randomly divided into four groups：control group（group A）,control ＋ escitalopram group （group B）,depressive group （group C）,and depressive ＋ escitalopram group （group D）.Chronic mild unpredicted stress （CUMS）with solitary condition was taken to establish rat depression model.And the group B and D were treated with intragastric admistration of escitalopram（10 mg · kg-1 · d-1）,the group A and C with sodium chloride.The open-field test and sucrose consumption were used to evaluate the depression behaviors of rats.The apoptotic hippocampal cells were detected by TUNEL.And the expression of GDNF,Bax,Bcl-2 and Caspase3 mRNA were detected by real-time RT-PCR.Results ① Compared with group A（12.0 ± 1.83）,the number of apoptotic cells in hippocampus was significantly increased in group C （19.3 ± 1.77） （P 〈 0.01）,while group B （11.9 ± 1.91） was no significant difference （P〉 0.05）.Compared with group C,the group D（12.7 ± 1.77） had a significant reduction in the number of apoptotic cells （P 〈 0.01）.②Compared with group A,GDNF and Bcl-2 mRNA expression was decreased （P 〈 0.01）,but Bax and Caspase3 mRNA expression was both increased significantly in group C（P〈0.01） ;while in group D,GDNF and Bcl-2 mRNA expression was higher （P 〈0.01）,but Bax and Caspase3 mRNA expression was lower than that in group C （P 〈0.01）.Conclusion Escitalopram can improve depressive behaviors and reduce hippocampal apoptosis,which maybe associate with increasing GDNF protein and mRNA expression,and promoting the regeneration of neurons,up-regulating of mRNA Bcl-2 expression,and down-regulating of mRNA Bax and Caspase3 expression.Finally it may prevent the neuronal apoptosis in hippocampal and play the role of cerebral protection.