目的:从皮质酮-炎性反应-线粒体网络动态变化研究抑郁症肝郁脾虚病机及醒脾解郁方干预效应。方法:采用6周慢性不可预见性温和应激(CUMS)方法建立抑郁症肝郁脾虚大鼠模型,应激同时灌胃给药。于2、4、6周末采集各组血清,ELISA法检测皮质酮(CORT)、肿瘤坏死因子-α(TNF-α)、干扰素-γ(IFN-γ)、白介素-4(IL-4)、白介素-6(IL-6)及白介素-10(IL-10)含量,于2、6周末行前额叶、肝脏取材,透射电镜观察线粒体形态。结果:应激2周时,CUMS大鼠出现CORT、TNF-α、IFN-γ、IL-6含量显著升高(P<0.01),IL-10含量显著降低(P<0.05),前额叶神经元、肝细胞线粒体轻微损伤;应激6周时,CUMS大鼠出现CORT、TNF-α、IFN-γ、IL-6含量显著升高(P<0.01),IL-4、IL-10含量显著降低(P<0.01),前额叶神经元、肝细胞线粒体明显损伤。中药醒脾解郁方可早期拮抗CORT升高,抑制炎性反应及线粒体损伤。结论:应激早期可致CORT含量显著升高及炎性反应网络部分紊乱,应激后期皮质酮-炎性反应-线粒体网络明显失衡,表现为抑郁症肝郁脾虚证,中药保护作用明显。

Abstract: Objective: To study the pathogenesis of stagnation of liver qi and spleen deficiency and the effect of Xingpi Jieyu Decoction on depression based on the changes in corticosterone-inflammation-mitochondrial network. Methods: A 6-week chronic unpredictable mild stress (CUMS) method was used to establish a rat model of depression which met the syndrome of stagnation of liver qi and spleen deficiency. The serum was collected at end of the 2nd, 4th and 6th week, and the levels of CORT, TNF-α, IFN-γ, IL-4, IL-6 and IL-10 in serum were detected by Elisa. At 2 and 6 weeks, the prefrontal cortex and the liver tissue were harvested for the observation of the mitochondrial ultrastructure under transmission electron microscopy. Results: The levels of CORT, TNF-α, IFN-γ and IL-6 in serum were significantly increased (P<0.01) and IL-10 levels decreased (P<0.05) when rats were suffered from 2-week CUMS. Meanwhile, the mitochondria in the neuron of prefrontal cortex and the liver cell were slightly damaged. The levels of CORT, TNF-α, IFN-γ and IL-6 in serum were significantly increased (P<0.01) and the levels of IL-4 and IL-10 were significantly decreased (P<0.01) when rats were suffered from 6-week CUMS. Meanwhile, the mitochondria in the neuron of the prefrontal cortex and the liver cell were obviously damaged. Xingpi Jieyu Decoction early antagonized the increase of corticosterone and inhibited inflammation and mitochondrial damage. Conclusion: The CORT content is increased obviously and the inflammatory network is partially disturbed at the early stage of stress. The corticosterone-inflammation-mitochondrial network was imbalanced obviously at the late stage of stress, which manifested the syndrome of stagnation of liver qi and spleen deficiency. The Chinese medicine compound formula Xingpi Jieyu Decoction played obvious protective effect on the stressed rats.