Impact of hyperoside on the blood-brain barrier in rats with bacterial meningitis through the microRNA-155/BDNF pathway.

IF 3.2 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Neuroendocrinology Pub Date : 2025-07-04 DOI:10.1159/000547276

Tao Zhang, Long Zhao, Renzhao Kuang

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引用次数: 0

Abstract

Objective: This study aims to elucidate the effect and mechanism of hyperoside on blood-brain barrier (BBB) damage in bacterial meningitis (BM) by regulating the microRNA-155 (miR-155)/brain-derived neurotrophic factor (BDNF) pathway.

Methods: A rat model of meningitis was established via intracisternal injection of Streptococcus pneumoniae (SPN), while an in vitro BBB injury model was created by treating human cerebral microvascular endothelial cells (hCMEC/D3) with lipopolysaccharide (LPS). Hyperoside was administered in both models. Evans blue staining assessed BBB permeability in rats. Brain water content was determined using the wet-dry weight method. Transendothelial electrical resistance (TEER) was measured with an endothelial resistance meter. RT-qPCR, Western blot (WB), and ELISA assessed the expression of tight junction proteins in brain tissues and cell supernatants. ELISA was also used to measure inflammatory cytokine in cerebrospinal fluid and cell culture supernatants. Bioinformatics analysis and dual-luciferase reporter assays validated the regulatory relationship between miR-155 and BDNF.

Results: Hyperoside treatment reduced BBB permeability, alleviated brain edema, and suppressed inflammatory cytokine expression in SPN-infected rats. In LPS-induced hCMEC/D3 cells, hyperoside significantly increased TEER values. Hyperoside markedly downregulated miR-155 and upregulated BDNF expression. miR-155 directly targeted BDNF and negatively regulated its expression in hCMEC/D3 cells. Importantly, the administration of a miR-155 mimic or BDNF knockdown (sh-BDNF) partially reversed the protective effects of hyperoside on TEER, tight junction protein expression (ZO-1, claudin-5, AQP4), and inflammatory cytokine levels (TNF-α, IL-1β, IL-6) in LPS-induced hCMEC/D3 cells.

Conclusion: Hyperoside mitigates BBB damage in BM via reducing miR-155 expression and upregulating BDNF expression, leading to an increase in tight junction-related protein expression, a reduction in inflammatory factor secretion, and a decrease in BBB permeability.

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金丝桃苷通过microRNA-155/BDNF通路对细菌性脑膜炎大鼠血脑屏障的影响

目的：本研究旨在阐明金丝桃苷通过调控microRNA-155 (miR-155)/脑源性神经营养因子（BDNF）通路对细菌性脑膜炎（BM）血脑屏障（BBB）损伤的作用及机制。方法：采用脑内注射肺炎链球菌（SPN）建立大鼠脑膜炎模型，脂多糖（LPS）处理人脑微血管内皮细胞（hCMEC/D3）建立体外血脑屏障损伤模型。两种模型均给予金丝桃苷。Evans蓝染色评估大鼠血脑屏障通透性。采用干湿重法测定脑含水量。用内皮电阻计测定跨内皮电阻（TEER）。RT-qPCR、Western blot （WB）和ELISA检测脑组织和细胞上清液中紧密连接蛋白的表达。ELISA法测定脑脊液和细胞培养上清液中炎性细胞因子。生物信息学分析和双荧光素酶报告基因检测证实了miR-155和BDNF之间的调控关系。结果：金丝桃苷治疗可降低spn感染大鼠血脑屏障通透性，减轻脑水肿，抑制炎症细胞因子表达。在lps诱导的hCMEC/D3细胞中，金丝桃苷显著提高TEER值。金丝桃苷显著下调miR-155，上调BDNF表达。miR-155直接靶向BDNF，负向调控其在hCMEC/D3细胞中的表达。重要的是，在lps诱导的hCMEC/D3细胞中，miR-155模拟物或BDNF敲低（sh-BDNF）的管理部分逆转了金丝桃苷对TEER、紧密连接蛋白表达（ZO-1、cladin -5、AQP4）和炎症细胞因子水平（TNF-α、IL-1β、IL-6）的保护作用。结论：金丝桃苷通过降低miR-155表达和上调BDNF表达，导致紧密连接相关蛋白表达增加，炎症因子分泌减少，血脑屏障通透性降低，从而减轻脑梗死血脑屏障损伤。

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来源期刊

Neuroendocrinology 医学-内分泌学与代谢

CiteScore

8.30

自引率

2.40%

发文量

审稿时长

6-12 weeks

期刊介绍： ''Neuroendocrinology'' publishes papers reporting original research in basic and clinical neuroendocrinology. The journal explores the complex interactions between neuronal networks and endocrine glands (in some instances also immunecells) in both central and peripheral nervous systems. Original contributions cover all aspects of the field, from molecular and cellular neuroendocrinology, physiology, pharmacology, and the neuroanatomy of neuroendocrine systems to neuroendocrine correlates of behaviour, clinical neuroendocrinology and neuroendocrine cancers. Readers also benefit from reviews by noted experts, which highlight especially active areas of current research, and special focus editions of topical interest.