丹参素钠对慢性不可预知温和应激模型小鼠的抗抑郁作用  

Anti-depressant effects of Tanshinol Sodium in chronic unpredicted mild stress mice

作　　者：钟淑娟[1] 郑思超[1] 丘秀玉 朱莉娜[1] ZHONG Shu-juan;ZHENG Si-ehao;QIU Xiu-yu;ZHU Li-na(The Fifth Affiliated Hospital of Guangzhou Medical University,Guangzhou 510700,China)

机构地区：[1]广州医科大学附属第五医院,广州510700

出　　处：《中国新药杂志》2018年第23期2819-2824,共6页Chinese Journal of New Drugs

基　　金：广州医科大学博士科研启动基金(2016034)

摘　　要：目的:探讨丹参素钠对慢性不可预知温和应激(chronic unpredicted mild stress,CUMS)模型小鼠的抗抑郁作用。方法:采用慢性不可预知温和应激方法建立小鼠抑郁症模型,造模成功后,连续灌胃(ig)给予丹参素钠(10,20和40 mg·kg^(-1))或氟西汀(10 mg·kg^(-1))或溶剂3周。采用旷场实验、糖水偏爱实验、强迫游泳实验和悬尾实验检测小鼠抑郁样行为的变化; ELISA法检测小鼠血浆促肾上腺皮质激素(ACTH)和皮质酮(CORT)的浓度; HPLC法测定小鼠海马组织5-羟色胺(5-HT)、去甲肾上腺素(NE)和多巴胺(DA)的含量。结果:抑郁样行为学评测结果显示,与正常对照组相比,CUMS模型组小鼠水平运动和垂直运动得分降低(P <0. 001)、糖水偏爱度显著下降(P <0. 001)、强迫游泳不动时间和悬尾不动时间明显延长(P <0. 001),而丹参素钠(20和40 mg·kg^(-1))给药3周明显改善CUMS小鼠上述抑郁样行为; ELISA检测结果显示,丹参素钠可显著性减少ACTH和CORT在CUMS小鼠血浆中的含量; HPLC结果显示,丹参素钠可明显增加CUMS小鼠海马内5-HT,NE和DA的含量; Western Blot结果显示,丹参素钠可明显增加CUMS小鼠海马p-CREB和BDNF的蛋白表达。结论:丹参素钠能明显改善CUMS所致的小鼠抑郁样行为,且该作用可能与其抑制下丘脑-垂体-肾上腺(HPA)轴功能亢进和增加海马内单胺类神经递质的含量及激活CREB/BDNF通路有关。Objective: To investigate the anti-depressant effect of Tanshinol Sodium( TS) in chronic unpredictable mild stress( CUMS) mice. Methods: The depression-like mice model is established using chronic unpredicted mild stress. The successfully established experimental mice are continuously administrated with TS( 10,20,40 mg·kg^-1) or Fluoxetine( 10 mg·kg^-1) or vehicle for 21 days. Open-field test( OFT),sucrose preference test( SPT),forced swim test( FST) and tail suspension test( TST) are used to evaluate the anti-depressant effects of TS. Enzyme-linked immunosorbent assay( ELISA) is used to examine the concentration of Adrenocorticotropic hormone( ACTH) and corticosterone( CORT) in plasma of mice. The content of hippocampal 5-hydroxytryptamine( 5-HT),norepinephrine( NE) and Dopamine( DA) is detected by high performance liquid chromatography( HPLC). Results: Depression-like behavioral evaluation showed that significant changes of crossing scores and rearing scores,sucrose preference index in SPT,immobility time in FST and TST were observed in CUMS mice compared with the normal control group( P < 0. 001). However,the depression-like behaviors mentioned above in CUMS mice were reversed evidently by Tanshinol Sodium( TS) at doses of 20 and 40 mg·kg^-1 after 3 weekstreatment. ELISA test showed that TS could significantly inhibit the secretion of ACTH and CORT in the plasma of CUMS mice. Result of HPLC suggested that TS significantly increased the contents of 5-HT,NE and DA in hippocampus of CUMS mice. Result of Western bot showed that TS significantly increased the protein expression of p-CREB and BDNF in hippocampus of CUMS mice. Conclusion: TS can improve the depression-like behaviors of CUMS mice obviously,which may be related to the inhibition of HPA axis hyperfunction,the increased content of monoamines neurotransmitters and activation of CREB/BDNF signaling pathway in hippocampus.

关 键 词：丹参素钠 抑郁 慢性不可预知温和应激 

分 类 号：R965.1[医药卫生—药理学] R975.5[医药卫生—药学]