四逆散对抑郁模型大鼠HPA轴、海马BDNF及其受体TrKB的影响

Effects of Sini San on HPA Axis and Expression of BDNF and TrKB in Hippocampus of Depression Model Rats

摘要:

目的：探讨四逆散的高、低剂量组对抑郁模型大鼠下丘脑-垂体-肾上腺轴（HPA轴）、海马脑源性神经营养因子（BDNF）及其受体型酪氨酸激酶B（TrKB）表达的影响。方法：SD雄性大鼠50只，随机分为正常对照组、模型组、盐酸文拉法辛组（12.5 mg·kg^-1）、四逆散高、低剂量组（10，5 g·kg^-1）。采用慢性轻度不可预见性刺激造模，同时ig给药21 d后分别取血、下丘脑和海马。采用放射免疫分析法检测大鼠血浆皮质醇（CORT）、促肾上腺皮质激素（ACTH）及下丘脑中促肾上腺皮质激素释放激素（CRH）的含量变化，采用免疫组化分析法检测海马BDNF及其TrKB阳性神经元面密度值的变化。结果：与正常组相比，模型组大鼠血浆中CORT，ACTH及下丘脑CRH的含量明显升高，海马中BDNF和TrKB的神经面密度值明显降低。与模型组相比，四逆散高、低剂量组可以显著降低抑郁症模型大鼠血浆CORT，ACTH、下丘脑CRH的含量；增加大鼠海马BDNF及其TrKB阳性神经元面密度值。结论：四逆散可明显改善抑郁模型大鼠的抑郁状态，其机制可能是通过HPA轴增加海马BDNF，TrKB的表达。

Abstract:

Objective: To investigate the effects of Sini San on hypothalamic pituitary adrenal axis (HPA axis) and expression of brain-derived neurotrophic factor (BDNF) and tyrosine kinase B(TrKB)in hippocampus of the depression model rats. Method: Fifty male SD rats were randomly divide into five groups:control group,model group,Venlafaxine hydrochloride group(12.5 mg·kg^-1),two concentration of sinisan groups(10,5 g·kg^-1). The rats accepted 21 days both chronic mild unexpected stimulation and intragastric administration,and then,drawn blood,taken hypothalamus,taken hippocampus. To detect the content changes of the rats' plasma cortisol (CORT),adrenocorticotropic hormone (ACTH) and hypothalamic corticotropin releasing hormone (CRH)by the radioimmunoassay. Using the immunohistochemical analysis method to test the positive neurons surface density values' change of the BDNF and TrKB in the hippocampus. Result: Compared with the control group,the rats in model group significantly increased the contents of the plasma CORT,ACTH and hypothalamic CRH,and decreased the positive neurons surface density values of the BDNF and TrKB in the hippocampus. Compared with the model group,Sini San high and low dose group could significantly decrease the content of the depression model rats' plasma CORT,ACTH and hypothalamic CRH;and increase positive neurons surface density values of the BDNF and TrKB in the hippocampus. Conclusion: Sini San can obviously improve depressive state of the rats,which mechanism may berelated with increasing the expression of BDNF and TrKB in hippocampus by the HPA.