还少丹对抑郁模型大鼠HPA轴功能和行为学的影响

Effects of Huanshao Dan on HPA Axis Function and Behavior of Depression Model Rats

目的:观察抑郁模型大鼠下丘脑-垂体-肾上腺(Hypothalamic-pituitary-adrenal,HPA)轴功能和行为学的变化以及还少丹抗抑郁的可能机制。方法:将70只雌雄各半的大鼠随机分成正常对照组16只,造模组54只。正常对照组正常饲养,造模组采用慢性不可预知温和应激法结合孤养21 d建立抑郁大鼠模型,造模成功后分成模型对照组、还少丹0.81、1.62、3.24 g/kg组和盐酸氟西汀胶囊1.8 mg/kg组。分别予以相应药物灌胃干预,并每周测一次行为学指标。药物干预21 d后,分别采用酶联免疫吸附法(Enzyme Linked Immunosorbent Assay,ELISA)和逆转录-聚合酶链反应(RT-PCR)检测大鼠脑组织5-羟色胺(5-HT)、去甲肾上腺素(NE)、多巴胺(DA)和促肾上腺皮质激素(ACTH)、皮质醇(CORT)含量和mRNA的表达。结果:与正常对照组比较,模型对照组大鼠敞箱实验得分、糖水偏好度均明显降低,其脑组织内5-HT、NE、DA的含量显著降低而Acth、Cort的mRNA表达水平显著上调(P<0.01);与模型对照组相比,还少丹0.81、1.62、3.24 g/kg组和盐酸氟西汀胶囊1.8 mg/kg组敞箱实验得分和糖水偏好度均明显升高,其脑组织内5-HT、NE、DA的含量均明显升高且Acth、Cort的mRNA表达明显下调(P<0.05或P<0.01)。结论:还少丹能提高抑郁大鼠脑内单胺类神经递质的含量并下调Acth、Cort的mRNA表达,其抗抑郁的机制可能与增加单胺类神经递质和改善HPA轴功能亢进有关。

Objective:To observe the changes in hypothalamic pituitary adrenal(HPA)axis function and behaviors of depression model rats,and explore the possible mechanism of Huanshao Dan in anti-depression.Methods:Seventy rats(half males and half females)were randomly divided into the blank control group(n=16)and modeling group(n=54).The rats in the blank control group were fed normally,while those in the modeling group were exposed to chronic unpredictable mild stress combined with isolated rearing for 21 d for inducing depression.After successful modeling,the rats were then divided into the model control group,0.81 g/kg,1.62 g/kg,and 3.24 g/kg Huanshao Dan groups,and 1.8 mg/kg fluoxetine hydrochloride capsule group,and treated with intragastric administration of the corresponding drugs.Their behavioral indicators were measured once every week.After 21 d of drug intervention,the content and mRNA expression of 5-hydroxytryptamine(5-HT),norepinephrine(NE),dopamine(DA),adrenocorticotropic hormone(ACTH),and cortisol(CORT)were detected by enzyme linked immunosorbent assay(ELISA)and reverse transcriptase polymerase chain reaction(RT-PCR),respectively.Results:Compared with the blank control group,the model control group exhibited significantly decreased open field test score and sucrose water preference,lowered 5-HT,NE,and DA content in brain tissue,and up regulated mRNA expression of ACTH and CORT(P<0.01).Compared with the model control group,Huanshao Dan at 0.81 g/kg,1.62 g/kg,and 3.24 g/kg and 1.8 mg/kg fluoxetine hydrochloride capsule all remarkably elevated the open field test score and sucrose water preference,increased 5-HT,NE,and DA content in the brain tissue,and down regulated the mRNA expression levels of ACTH and CORT(P<0.01 or P<0.05).Conclusion:Huanshao Dan is able to increase the content of monoamine neurotransmitters and down regulate the mRNA expression of ACTH and CORT in depressed rats,and its anti-depression mechanism may be related to the increase in monoamine neurotransmitters and improvement of HPA axis function.