电针对抑郁大鼠海马组织CREB/BDNF/TrkB信号通路的影响

Electroacupuncture on hippocampal CREB/BDNF/TrkB in depressive rats effects of signaling pathways

目的:探讨电针对抑郁大鼠海马组织CREB/BDNF/TrkB信号通路的影响。方法:采用孤养结合慢性不可预知应激(CUMS)方法建立抑郁大鼠模型,随机分为空白组、模型组、电针组、氟西汀组,每组10只。电针组选取“百会”、“神庭”、“合谷”、“太冲”,每日造模前1 h针刺,留针20 min,1次/d,持续21 d;氟西汀组:每日造模前1 h氟西汀(10 mg/kg,1 mg/mL)灌胃给药,持续21 d。观察大鼠的体质量变化、旷场实验的站立次数和运动距离、强迫游泳实验的不动时间,ELISA法检测血清5⁃HT、DA、NE的含量;Western blot检测海马组织中BDNF、CREB、TrkB的表达;实时荧光定量PCR检测海马组织中BDNF、CREB mRNA的表达。结果:造模干预后:与空白组比较,模型组大鼠体质量、站立次数、运动距离、血清5⁃HT、DA、NE的含量、海马组织中BDNF、CREB、TrkB的表达显著下降(均P<0.01),不动时间显著升高(P<0.01);与模型组比较,电针组、氟西汀组大鼠体质量、站立次数、运动距离、血清5⁃HT、DA、NE的含量、海马组织中BDNF、CREB、TrkB的表达显著升高(均P<0.05),不动时间显著显著降低(P<0.05);电针组和氟西汀组比较,各指标差异均无统计学意义(P>0.05)。结论:电针能够显著改善大鼠的抑郁症状,其机制可能与调控海马组织中BDNF/TrkB/CREB信号通路相关蛋白和提高单胺类神经递质5⁃HT、NE和DA的含量有关,从而产生抗抑郁作用。

Objective:To investigate the effect of electroacupuncture on CREB/BDNF/TrkB signaling pathway in hippo⁃campus of depressed rats.Methods:The depression rat model was established by chronic unpredictable stress(CUMS)combined with solitary rearing.The rats were randomly divided into blank group,model group,electroacupuncture group and fluoxetine group,with 10 rats in each group.In the electroacupuncture group,'Baihui','Shenting','Hegu'and'Taichong'were selected.Acu⁃puncture was performed 1 h before modeling every day,and the needles were retained for 20 min,once a day for 21 days.Fluox⁃etine group:Fluoxetine(10 mg/kg,1 mg/mL)was intragastrically administered 1h before modeling for 21 days.The changes of body weight,the number of standing and the distance of movement in open field test,the immobility time of forced swimming test were observed.The contents of 5⁃HT,DA and NE in serum were detected by ELISA.The expression of BDNF,CREB and TrkB in hippocampus was detected by Western blot.The expression of BDNF and CREB mRNA in hippocampus was detected by real⁃time fluorescence quantitative PCR.Results:After modeling intervention:Compared with the blank group,the body weight,the number of standing,the distance of movement,the content of serum 5⁃HT,DA and NE,the expression of BDNF,CREB and TrkB in the hippocampus of the model group were significantly decreased(all P<0.01),and the immobility time was signifi⁃cantly increased(P<0.01).Compared with the model group,the body weight,the number of standing,the distance of move⁃ment,the content of 5⁃HT,DA and NE in serum,the expression of BDNF,CREB and TrkB in hippocampus were significantly increased(all P<0.05),and the immobility time was significantly decreased(P<0.05)in the EA group and fluoxetine group.There was no significant difference between the electroacupuncture group and the fluoxetine group(P>0.05).Conclusion:EA can significantly improve the symptoms of depression in rats,and its mechanism may be related to the regulation of BDNF/TrkB/CREB signaling pathway⁃related proteins in hippocampus,increase the content of monoamine neurotransmitters 5⁃HT,NE and DA,resulting in antidepressant effect.