Cerebrospinal fluid proteomics reveal potential protein targets of JiaWeiSiNiSan in preventing chronic psychological stress damage.
Cerebrospinal fluid proteomics reveal potential protein targets of JiaWeiSiNiSan in preventing chronic psychological stress damage.
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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标
DOI：
10.1080/13880209.2021.1954666
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发表时间：
2021-12
影响因子：
3.8
通讯作者：
Wu LL
中科院分区：
文献类型：
--
作者：
Wang HZ;Luo WL;Zeng NX;Li HZ;Li L;Yan C;Wu LL
摘要中药复方加味四逆散在临床上被广泛用于预防应激性神经精神疾病，并被证明对大鼠具有治疗性抗应激作用。然而，其机制仍不清楚。目的基于脑脊液蛋白质组学研究，探讨加味四逆散提高应激恢复能力、预防应激损伤的可能机制及作用靶蛋白。材料与方法采用6周慢性不可预见性轻度应激（CWS）模型，观察加味四逆散对大鼠心理应激恢复能力的影响。应用TMT蛋白质组学和生物信息学技术对脑脊液差异表达蛋白进行筛选和分析。平行反应监测（PRM）用于验证目标DEP。结果与对照组相比，加味四逆散组大鼠的蔗糖偏好性、T-迷宫的自主活动水平和准确性显著降低，不动时间显著延长，而加味四逆散组大鼠的上述抑郁样行为明显改善。定量蛋白质组学和生物信息学分析结果显示，加味四逆散能显著降低BNS大鼠CSF中Rps 4x、HSP 90 AA 1、Rps 12、Uba 1、Rsp 14、Tuba 1b的表达（p < 0.05，FDR < 0.5）。免疫荧光结果显示，与模型组相比，加味四逆散组大鼠海马齿状回（DG）BrdU/DCX阳性细胞数（p <0.01）和神经元相对数（p < 0.01）明显增加。结论加味四逆散可通过调节CSF中蛋白质的表达，提高应激恢复力，预防应激损伤。本研究为进一步研究预防精神疾病的中药方剂提供了科学依据。
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.
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