Role of TRIP6 in the progression of depression：regulating the function of brain microvascular endothelial cells and blood-brain barrier dysfunction

Yu Shoufen; Li Xiaosa; Wang Rong; Liu Junchang

doi:10.13406/j.cnki.cyxb.004034

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Role of TRIP6 in the progression of depression：regulating the function of brain microvascular endothelial cells and blood-brain barrier dysfunction

Frontiers in brain science and neuropsychiatric disorders | 更新时间：2026-04-15

- Role of TRIP6 in the progression of depression：regulating the function of brain microvascular endothelial cells and blood-brain barrier dysfunction
- Journal of Chongqing Medical University Vol. 51, Issue 4, Pages: 451-458(2026)
- 作者机构：
  
  空军军医大学西京医院心身科，西安 710032
- 作者简介：
- 基金信息：
- DOI：10.13406/j.cnki.cyxb.004034
  CLC： R749
- Received：09 June 2025，
  
  Revised：2026-01-16，
  
  Accepted：02 March 2026，
  
  Published：28 April 2026
- 稿件说明：
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余寿芬，李小飒，王蓉，等.甲状腺激素受体相互作用蛋白6参与抑郁症进展中BMVECs功能和血脑屏障功能紊乱调控的探究[J].重庆医科大学学报，2026，51（4）：451-458.

Yu Shoufen,Li Xiaosa,Wang Rong,et al.Role of TRIP6 in the progression of depression：regulating the function of brain microvascular endothelial cells and blood-brain barrier dysfunction[J].Journal of Chongqing Medical University,2026,51(4):451-458.
余寿芬，李小飒，王蓉，等.甲状腺激素受体相互作用蛋白6参与抑郁症进展中BMVECs功能和血脑屏障功能紊乱调控的探究[J].重庆医科大学学报，2026，51（4）：451-458. DOI： 10.13406/j.cnki.cyxb.004034.

Yu Shoufen,Li Xiaosa,Wang Rong,et al.Role of TRIP6 in the progression of depression：regulating the function of brain microvascular endothelial cells and blood-brain barrier dysfunction[J].Journal of Chongqing Medical University,2026,51(4):451-458. DOI： 10.13406/j.cnki.cyxb.004034.

摘要

目的

探讨甲状腺激素受体相互作用蛋白6（thyroid hormone receptor interactor 6，TRIP6）在重症抑郁症（major depressive disorder，MDD）进展过程中的调控作用和机制。

方法

将20只小鼠随机分为2组：对照组和慢性不可预知应激（chronic unpredictable mild stress，CUMS）组，每组10只。模型组使用CUMS方法构建MDD小鼠模型，随后进行行为学实验。取出各组小鼠的脑组织，通过分离培养得到原代脑微血管内皮细胞（brain microvascular endothelial cells，BMVECs），之后使用脂多糖（lipopolysaccharide，LPS）诱导BMVECs作为体外MDD模型。通过实时荧光定量聚合酶链式反应（quantitative real-time polymerase chain reaction，qRT-PCR）和蛋白免疫印迹法检测TRIP6在小鼠脑组织以及LPS诱导的BMVECs中的表达。四唑盐比色法（methylthiazolyldiphenyl-tetrazolium bromide，MTT）实验和流式细胞术分别检测LPS诱导的BMVECs的活力和凋亡。随后，使用Transwell小室构建了血脑屏障（blood-brain barrier，BBB）体外共培养模型，分析BBB共培养系统中的BBB渗透性、跨内皮电阻（transendothelial electrical resistance，TEER）以及BMVECs紧密连接蛋白的表达。

结果

强迫游泳实验（forced swim test，FST）和悬尾实验（tail suspension test，TST）结果表明，CUMS组小鼠的静止时间（TST和FST）均明显高于对照组（

0.05）；CUMS组小鼠的蔗糖偏好、中心区域停留

时间则明显低于对照组（

0.05），而2组间小鼠的总体运动距离差异无统计学意义（

0.05）。进一步研究表明TRIP6在MDD小鼠脑组织和BMVECs中的表达明显降低（

0.05）。此外，TRIP6过表达提高LPS诱导的BMVECs的细胞活力和迁移并抑制细胞凋亡（

0.05）。同时，过表达TRIP6降低了BBB渗透性，并提高BBB系统的TEER跨膜电阻并促进闭合蛋白（occludin，OCLN）、靠停蛋白5（claudin5，CLDN5）、紧密连接蛋白-1（zonula occludens-1，ZO-1）的表达（

0.05）。

结论

过表达TRIP6缓解了LPS诱导的BMVECs细胞功能损伤，并降低了BBB的渗透性，改善了紧密连接能力，说明TRIP6是调控MDD病理进程中BBB稳定性的关键调节因子。

Abstract

Objective

To explore the role of thyroid hormone receptor interactor 6（TRIP6） in the progression of major depressive disorder（MDD） and the underlying mechanisms.

Methods

Twenty mice were randomly divided into control group and model group，with 10 mice in each group. In the model group，a mouse MDD model was prepared using the chronic unpredictable mild stress method，followed by behavioral experiments for verification. The brain tissue of each mouse was obtained to isolate and culture primary brain microvascular endothelial cells（BMVECs）. An

in vitro

MDD model was established using lipopolysaccharide（LPS）-induced BMVECs. The expression of TRIP6 in mouse brain tissue and LPS-induced BMVECs was measured by quantitative real-time PCR and Western blot. The viability and apoptosis of LPS-induced BMVECs were assessed by MTT assay and flow cytometry，respectively. Subsequently，an

in vitro

co-culture-based blood-brain barrier（BBB） model was constructed using Transwell chambers. The permeability，transepithelial-transendothelial electrical resistance（TEER），and expression of tight junction proteins of the BBB system were measured.

Results

In both the forced swim test and tail suspension test，the resting time was significantly longer in the model group than in the control group（

0.05）. The model group showed a significantly lower sucr

ose preference level and a significantly shorter time spent in the central zone than the control group（

0.05），with no significant difference in the total distance traveled between the two groups （

0.05）. The expression of TRIP6 was significantly reduced in the brain tissue and BMVECs of MDD mice （

0.05）. TRIP6 overexpression significantly increased the viability and migration and inhibited the apoptosis of LPS-induced BMVECs （

0.05）. Meanwhile，for the BBB system，overexpressing TRIP6 significantly reduced its permeability，significantly increased TEER，and significantly upregulated the expression of tight junction proteins including occludin，claudin5，and zonula occludens-1 （

0.05）.

Conclusion

TRIP6 overexpression alleviates the functional damage of LPS-induced BMVECs，reduces the permeability of BBB，and improves the tight junction of BBB，indicating that TRIP6 is a key regulatory factor for BBB stability in the pathological process of MDD.

关键词

Keywords

references

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Department of Psychiatry，Xijing Hospital，The First Affiliated Hospital of Air Force Medical University

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