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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。
Objective: To investigate the effects of high and low doses of Sini Powder on hypothalamus-pituitary-adrenal axis (HPA axis), brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase B TrKB) expression. Methods: Fifty SD male rats were randomly divided into normal control group, model group, venlafaxine hydrochloride group (12.5 mg · kg -1), Sini San high and low dose group (10.5 g · kg- 1). Chronic mild unpredictable stimuli were used to establish models. At the same time, blood, hypothalamus and hippocampus were collected respectively after 21 d administration. Radioimmunoassay was used to detect the changes of plasma cortisol (CORT), adrenocorticotropic hormone (ACTH) and corticotropin-releasing hormone (CRH) in the hypothalamus. Immunohistochemistry was used to detect the levels of BDNF and its Changes of TrKB positive neuron densities. Results: Compared with the normal group, the levels of CORT, ACTH and hypothalamic CRH in the model group were significantly increased, and the neuronal density of BDNF and TrKB in the hippocampus was significantly decreased. Compared with the model group, the Sini San high and low dose groups could significantly reduce the levels of plasma CORT, ACTH and hypothalamus CRH in the depression model rats, and increase the density of BDNF and TrKB positive neurons in the hippocampus. Conclusion: Sini Decoction can significantly improve the depressive state of depression in rats, its mechanism may be through the HPA axis to increase the expression of BDNF and TrKB in the hippocampus.