Abstract

Context

Chinese herbal formula JiaWeiSiNiSan (JWSNS) has been widely used to prevent stress-induced neuropsychiatric ailments in clinics and proven to have therapeutic anti-stress effects on rats. However, the mechanism remains unclear.

Objective

Based on the proteomics of cerebrospinal fluid (CSF), this study explores the possible mechanism and target proteins of JiaWeiSiNiSan raising stress resilience and preventing stress damage.

Materials and methods

A 6-week Chronic Unpredictable Mild Stress (CUMS) model was applied on adult Wistar male rats to observe the effects of JWSNS on improving mental stress resilience. Tandem Mass Tag (TMT) proteomics and bioinformatics analysis were used to screen and analyze differentially expressed proteins (DEPs) in CSF. Parallel Reaction Monitoring (PRM) was used to validate target DEPs.

Results

Significantly decreased sucrose preference, locomotion activity level and accuracy of T-maze, as well as increased immobility time, were observed in CUMS rats compared to CON rats while JWSNS improved above depression-like behaviours. The quantitative proteomics and bioinformatics analysis showed that JWSNS decreased the expression of Rps4x, HSP90AA1, Rps12, Uba1, Rsp14, Tuba1b in CUMS rats CSF (p < 0.05, FDR < 0.5). Immunofluorescence results showed that the number of BrdU/DCX positive cells (p < 0.01) and the relative number of neurons (p < 0.01) in the hippocampus dentate gyrus (DG) of the JSWNS group significantly increased, compared with the CUMS group.

Conclusions

JWSNS could increase mental stress resilience and prevent stress damage by regulating proteins in CSF. This study provides a scientific basis for further study on Chinese formulas preventing mental illness.

中文翻译：

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脑脊液蛋白质组学揭示加味四逆散预防慢性心理应激损伤的潜在蛋白质靶点

摘要

语境

中草药配方加味四逆散 (JWSNS) 在临床上已被广泛用于预防压力引起的神经精神疾病，并被证明对大鼠具有治疗性抗压力作用。然而，机制仍不清楚。

客观的

本研究基于脑脊液（CSF）蛋白质组学，探讨加味四逆散提高应激恢复能力和预防应激损伤的可能机制和靶蛋白。

材料和方法

将 6 周慢性不可预测轻度压力 (CUMS) 模型应用于成年 Wistar 雄性大鼠，观察 JWSNS 对提高心理压力恢复能力的影响。串联质量标签 (TMT) 蛋白质组学和生物信息学分析用于筛选和分析 CSF 中的差异表达蛋白 (DEP)。平行反应监测 (PRM) 用于验证目标 DEP。

结果

与 CON 大鼠相比，在 CUMS 大鼠中观察到 T 迷宫的蔗糖偏好、运动活动水平和准确性显着降低，以及不动时间增加，而 JWSNS 改善了抑郁样行为。定量蛋白质组学和生物信息学分析表明，JWSNS降低了CUMS大鼠脑脊液中Rps4x、HSP90AA1、Rps12、Uba1、Rsp14、Tuba1b的表达（p  < 0.05，FDR < 0.5）。免疫荧光结果显示， 与CUMS组相比，JSWNS组海马齿状回（DG） BrdU/DCX阳性细胞数（ p  <0.01）和神经元相对数量（p <0.01）显着增加。

结论

JWSNS 可以通过调节脑脊液中的蛋白质来提高心理压力恢复能力并防止压力损伤。本研究为进一步研究预防精神疾病的方剂提供科学依据。