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五苓散调控proBDNF/p75NTR/ sortilin和BDNF/TrkB通路治疗溃疡性结肠炎合并抑郁症的机制

Mechanism of Wuling powder modulating proBDNF/p75NTR/sortilin and BDNF/TrkB pathways in the treatment of ulcerative colitis complicated with depression.

作者信息

Wang Jing-Jing, Fan Yi-Hong, Cao Wan-Ting, Huang Rong, Yao Xin-Yi, Li Meng-Lin

机构信息

Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310003, Zhejiang Province, China.

Department of Gastroenterology, Beilun District Hospital of Traditional Chinese Medicine, Ningbo 315800, Zhejiang Province, China.

出版信息

World J Gastroenterol. 2025 Feb 28;31(8):100227. doi: 10.3748/wjg.v31.i8.100227.

DOI:10.3748/wjg.v31.i8.100227
PMID:40062332
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11886523/
Abstract

BACKGROUND

Ulcerative colitis (UC) is a chronic inflammatory disease affecting the colon. The most common psychological issue in UC patients is varying degrees of depression, which affects the condition and quality of life of UC patients and may lead to deterioration of the patient's condition. UC drugs combined with antianxiety and antidepression drugs can alleviate symptoms of both depression and UC. Brain-derived neurotrophic factor (BDNF) precursor (proBDNF)/p75 neurotrophin receptor (p75NTR)/sortilin and BDNF/tropomyosin receptor kinase B (TrkB) signalling balance is essential for maintaining brain homeostasis and preventing the development of depressive behaviours.

AIM

To explore the mechanism by which Wuling powder regulates the proBDNF/p75NTR/sortilin and BDNF/TrkB pathways in the treatment of UC with depression.

METHODS

Depression was established in C57BL/6J mice chronic restraint stress, and the UC model was induced with dextran sodium sulfate (DSS). In the treatment stage, mesalazine (MS) was the basic treatment, Wuling powder was the experimental treatment, and fluoxetine was the positive control drug for treating depression. Changes in intestinal mucosal inflammation, behaviour, and the proBDNFp75NTR/sortilin and BDNF/TrkB pathways were evaluated.

RESULTS

In the depression groups, Wuling powder decreased the immobility time, increased the distance travelled in the central zone and the total distance travelled, and restored balance in the proBDNF/p75NTR/sortilin and BDNF/TrkB signalling pathways. In the DSS and chronic restraint stress + DSS groups, immobility time increased, distance travelled in the central zone and total distance travelled decreased, activity of the proBDNF/p75NTR/sortilin pathway was upregulated, and activity of the BDNF/TrkB pathway was downregulated, indicating that mice with UC often have comorbid depression. Compared with those of MS alone, Wuling powder combined with MS further decreased the colon histopathological scores and the expression levels of tumor necrosis factor-alpha and interleukin-6 mRNAs.

CONCLUSION

This study confirmed that Wuling powder may play an antidepressant role by regulating the balance of the proBDNF/p75NTR/sortilin and BDNF/TrkB signalling pathways and further relieve intestinal inflammation in UC.

摘要

背景

溃疡性结肠炎（UC）是一种影响结肠的慢性炎症性疾病。UC患者最常见的心理问题是不同程度的抑郁，这会影响UC患者的病情和生活质量，并可能导致患者病情恶化。UC药物联合抗焦虑和抗抑郁药物可缓解抑郁和UC的症状。脑源性神经营养因子（BDNF）前体（proBDNF）/p75神经营养因子受体（p75NTR）/sortilin和BDNF/原肌球蛋白受体激酶B（TrkB）信号平衡对于维持脑内稳态和预防抑郁行为的发生至关重要。

目的

探讨五苓散治疗UC伴抑郁时调节proBDNF/p75NTR/sortilin和BDNF/TrkB通路的机制。

方法

通过慢性束缚应激建立C57BL/6J小鼠抑郁模型，并用葡聚糖硫酸钠（DSS）诱导UC模型。在治疗阶段，美沙拉嗪（MS）为基础治疗，五苓散为实验治疗，氟西汀为治疗抑郁的阳性对照药物。评估肠道黏膜炎症、行为以及proBDNF/p75NTR/sortilin和BDNF/TrkB通路的变化。

结果

在抑郁组中，五苓散减少了不动时间，增加了在中央区域的行进距离和总行进距离，并恢复了proBDNF/p75NTR/sortilin和BDNF/TrkB信号通路的平衡。在DSS组和慢性束缚应激+DSS组中，不动时间增加，在中央区域的行进距离和总行进距离减少，proBDNF/p75NTR/sortilin通路的活性上调，BDNF/TrkB通路的活性下调，表明UC小鼠常伴有抑郁。与单独使用MS相比，五苓散联合MS进一步降低了结肠组织病理学评分以及肿瘤坏死因子-α和白细胞介素-6 mRNA的表达水平。

结论

本研究证实五苓散可能通过调节proBDNF/p75NTR/sortilin和BDNF/TrkB信号通路的平衡发挥抗抑郁作用，并进一步缓解UC的肠道炎症。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a25c/11886523/bce22f0d99ba/100227-g011.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a25c/11886523/bce22f0d99ba/100227-g011.jpg

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