目的 探讨滋水清肝饮在应用脂多糖(LPS)制备的小鼠抑郁模型中的抗抑郁作用和潜在机制。方法 选取60只小鼠按随机数字表随机分为6组:对照组、模型组、盐酸氟西汀组(阳性药,10 mg·kg^-1)和滋水清肝饮低、中、高剂量(8.835、17.670、35.340 g·kg^-1)组,给药14 d后,除对照组ip等量0.9 %的氯化钠溶液外,其余各组均ipLPS (0.83 mg·kg^-1),LPS注射结束24 h后,称小鼠质量,并进行悬尾实验和强迫游泳实验;通过苏木素-伊红(HE)染色观察小鼠海马形态学改变;免疫荧光染色检测海马小胶质细胞标志物离子化钙结合适配分子1(Iba-1)荧光强度;试剂盒法检测小鼠血清中超氧化物歧化酶(SOD)活力、丙二醛(MDA)、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、5-羟色胺(5-HT)水平及小鼠海马吲哚胺2,3-双加氧酶1(IDO1)、犬尿氨酸(KYN)、5-HT水平;Western blotting法检测小鼠海马组织中p-核因子κB (NF-κB)、p-细胞外调节蛋白激酶(ERK)蛋白表达。结果 与模型组相比,滋水清肝饮组小鼠体质量均有所回升(P<0.05);各给药组小鼠的悬尾实验和强迫游泳实验不动时间显著缩短(P<0.05、0.01);各给药组海马形态学转好,海马小胶质细胞标志物Iba-1表达显著降低(P<0.05);滋水清肝饮中、高剂量组和盐酸氟西汀组小鼠血清中的5-HT水平显著增加(P<0.05),各给药组血清SOD活力显著增强(P<0.05),血清TNF-α、IL-6、IL-1β、MDA水平显著降低(P<0.05、0.01);各给药组小鼠海马中IDO1、KYN水平显著下降(P<0.05、0.01),滋水清肝饮中、高剂量组和盐酸氟西汀组海马中5-HT水平显著上升(P<0.05、0.01);各给药组海马组织中p-ERK、p-NF-κB蛋白表达显著降低(P<0.05、0.01)。结论 滋水清肝饮显著改善急性LPS小鼠的抑郁样行为,其机制可能与抑制ERK/NF-κB通路、降低IDO1水平、改善神经炎症有关。

Objective The aim of this study was to investigate the antidepressant effect and potential mechanism of Zishui Qinggan Yin (ZSQGY) in the LPS-induced depression mice model. Methods A mouse depression model was established by LPS. A total of 60 mice were randomly selected and randomly divided into six groups according to the random number table, namely control group, model group, Flu group (10 mg·kg^-1), ZSQGY low, medium and high dose (8.835, 17.670, 35.340 g·kg^-1) groups. After 14 days of administration, the control group was injected with the same amount of normal saline. The other groups were ip injected with LPS (0.83 mg·kg^-1). After 24 h LPS injection, mice are weighed and the tail suspension test and forced swimming test were performed. The morphological changes of mice hippocampus were observed by HE staining and Nishi staining, and immunofluorescence staining was used to detect the fluorescence intensity of hippocampal microglia marker Iba-1. The activity of superoxide dismutase (SOD), malondialdehyde (MDA), tumor necrosis factor- α (TNF- α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and 5- hydroxytryptamine (5-HT) in serum of mice and the levels of IDO1, KYN, and 5-HT in the hippocampus of mice were detected by kits. The expression of p-NF-κB, p-ERK, and ERK protein level in mouse hippocampus was detected by Western blotting. Results Compared with model group, the body weight of mice in the ZSQGY group increased (P < 0.05). The immobility time in the tail suspension experiment and forced swimming experiment of mice in each treatment group was significantly shortened (P < 0.05, 0.01). The morphology of the hippocampus improved in each treatment group, and the expression of the hippocampal microglial cell marker Iba-1 was significantly reduced (P < 0.05). The levels of 5-HT in the serum of mice in the middle and high-dose groups of ZSQGY and the Flu group were significantly increased (P < 0.05), the activity of SOD in serum was significantly enhanced in each treatment group (P < 0.05), and the levels of TNF-α, IL-6, IL-1β, and MDA in serum were significantly decreased (P < 0.05, 0.01). The levels of IDO1 and KYN in hippocampus were significantly decreased in each treatment group (P < 0.05, 0.01), the level of 5- HT in hippocampus was significantly increased in medium-dose and high-dose ZSQGY group and fluoxetine hydrochloride group (P < 0.05, 0.01). The protein expressions of p-ERK and p-NF-κB in hippocampus were significantly decreased in each treatment group (P < 0.05, 0.01). Conclusion ZSQGY can significantly improve the depression-like behavior in LPS-induced mice and the mechanism may be related to down-regulating ERK/NF-κB signaling pathway and IDO1 level.

R965

陕西省陕西中医药大学校级科研课题项目(2021GP25);陕西省自然科学基础研究计划(2022JQ-918);国家自然科学基金项目(82304504)