电针对慢性应激抑郁大鼠海马转化生长因子β3和碱性成纤维细胞生长因子表达的影响

Effect of Electroacupuncture Intervention on Behavior Changes and Levels of Hippocampal Transforming Growth Factor beta 3 and Basic Fibroblast Growth Factor Proteins in Depression Rats

目的:观察电针对慢性应激模型大鼠海马转化生长因子β3(TGF-β3)、碱性成纤维细胞生长因子(bFGF)蛋白表达的影响,探讨电针对慢性应激抑郁模型大鼠海马神经的营养再生作用。方法:雄性SD大鼠随机分为空白组、模型组、电针组、氟西汀组,每组10只。除空白组外,其余组均采用慢性应激结合孤养方法造模28d。电针组于造模前1h选取"百会""印堂"穴进行电针,氟西汀组于造模前1h给予盐酸氟西汀混悬液5mL/kg灌胃治疗。通过旷场实验对大鼠进行行为学评价,采用生物素标记抗体芯片技术筛选出海马中差异蛋白TGF-β3、bFGF。结果:造模结束后,与空白组相比,模型组大鼠水平穿越格数、竖立次数均显著减少(P<0.01);与模型组相比,电针组和氟西汀组大鼠水平穿越格数、竖立次数均显著增加(P<0.01)。与空白组比较,模型组大鼠海马TGF-β3蛋白水平下降(fold change=0.48),bFGF蛋白水平上升(fold change=1.36);与模型组比较,电针组、氟西汀组TGF-β3蛋白水平上升(fold change=1.61,1.61),bFGF蛋白水平下降(fold change=0.61,0.45)。结论:电针可能通过上调TGF-β3蛋白表达水平参与促进神经血管的营养再生,并且良性调节具有神经保护作用的bFGF,使其趋于正常水平,从而改善慢性应激抑郁模型大鼠的行为学症状,这可能是针刺抗抑郁作用的分子机制之一。

Objective To observe the effect of electroacupuncture（EA）on behavior changes and the adundance levels of transforming growth factor beta 3（TGF-β3）and basic fibroblast growth factor（bFGF）proteins in the hippocampus of rats with chronic unpredictable mild stress（CUMS）-induced depression,so as to explore its mechanisms underlying improvement of depression.Methods Forty Sprague-Dawley rats were randomly divided into the following groups：control,model,EA,and medication（Fluoxetine）,n=10in each group.The depression model was established by CUMS combined with solitary raising for 28 days.EA（2Hz,0.6mA）was applied to＂Baihui＂（GV 20）and＂Yintang＂（GV 29）for 20 min,once daily before CUMS every day.The rats of the medication group were given with Fluoxetine（10mg/kg,5mL/kg）before CUMS every day.The behavioral changes（crossing and rearing locomotion）were detected by using open field tests.The expression levels of TGF-β3and bFGF proteins of the bilateral hippocampus tissues were detected using biotin label-based antibody protein chips.Results Compared to the control group,the crossed grid-square numbers and rearing times were significantly decreased in the model group（P0.01）.Following EA and medication interventions,the CUMS induced decreases of the crossed grid-square number and rearing times were notably reversed in both EA and medication groups（P0.01）,suggesting an amelioration of depression after the intervention.The relative expression level of hippocampal TGF-β3 was down-regulated（fold change=0.48,vs the control group）and that of bFGF up-regulated（fold change=1.36,vs the control group）in the model group.In both the EA and medication groups,the down-regulated TGF-β3expression and the up-regulated bFGF protein expression were suppressed（TGF-β3：fold change=1.61,1.61 and bFGF：fold change=0.61,0.45,vs the model group respectively）.Conclusion EA can improve the depression-like state in depression rats which may be associated with its effect in up-regulating hippocampal TGF-β3protein level and down-regulating bFGF protein expression via promoting neurogenesis.