血脑屏障中紧密连接蛋白-5在癫痫中的作用研究进展

陈静怡; 高凡凯; 薛国芳

doi:10.16766/j.cnki.issn.1674-4152.004099

血脑屏障中紧密连接蛋白-5在癫痫中的作用研究进展

doi: 10.16766/j.cnki.issn.1674-4152.004099

山西医科大学第二医院神经内科，山西太原 030001

基金项目:

山西省青年科技研究基金项目 202203021212056

详细信息

通讯作者:
薛国芳，E-mail：xueguofangty@163.com

中图分类号: R742.1 R338
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出版历程
- 收稿日期: 2025-01-23
- 网络出版日期: 2025-10-25

Advancements in the study of tight junction protein-5 in epilepsy within the blood-brain barrier

Department of Neurology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, China

摘要

摘要: 血脑屏障(BBB)由脑微血管内皮细胞构成，是一种重要的保护性屏障，能够限制血液中的有害物质进入大脑，维持脑组织稳定的内环境，其完整性对大脑功能至关重要。紧密连接蛋白是维持BBB结构和功能的关键成分，这些蛋白位于脑微血管内皮细胞之间，起到连接相邻细胞、保持屏障完整性的作用，构成一个高度调控的微环境。紧密连接蛋白-5(Claudin-5)是BBB中较为丰富的紧密连接蛋白之一，广泛分布于脑微血管内皮细胞的细胞膜上。有研究表明，Claudin-5在调控BBB的完整性和通透性方面起着至关重要的作用。它通过控制细胞之间的连接空隙，确保BBB的选择性和通透性，使得大脑能够得到所需的氧气、葡萄糖等物质，同时防止有害物质、病原体及其他潜在危害物质进入大脑。一旦Claudin-5的表达或功能发生异常，BBB的功能将受到影响, 从而引发一系列神经系统疾病，如神经炎症、脑血管疾病以及神经退行性疾病等。癫痫是一种由异常神经放电引起的疾病，部分研究表明Claudin-5可能通过改变BBB的通透性，影响脑组织内的离子浓度，进而参与癫痫的发病机制。尽管目前尚不完全清楚其具体机制，但Claudin-5的变化可能与癫痫的发生密切相关。综上，Claudin-5不仅在维持BBB的完整性方面起着至关重要的作用，也在中枢神经系统疾病，特别是癫痫的发病机制中具有潜在的研究价值。本文将综述Claudin-5的生理功能、病理变化以及在维持BBB完整性与癫痫中的作用，为癫痫疾病的治疗提供新的思路。
- 癫痫 /
- 血脑屏障 /
- 紧密连接 /
- 紧密连接蛋白-5
Abstract: The blood-brain barrier (BBB) is composed of brain microvascular endothelial cells. It is an important protective barrier that can limit the entry of harmful substances in the blood into the brain and maintain a stable internal environment of brain tissue. Its integrity is crucial to brain function. Tight junction proteins are key components in maintaining the structure and function of the BBB. These proteins are located between brain microvascular endothelial cells, connecting adjacent cells, and maintaining barrier integrity, forming a highly regulated microenvironment. Claudin-5 is one of the most abundant tight junction proteins in the BBB and is widely distributed on the cell membrane of brain microvascular endothelial cells. Studies have shown that Claudin-5 plays a crucial role in regulating the integrity and permeability of the BBB. It ensures the selective permeability of the BBB by controlling the connection gaps between cells, allowing the brain to obtain the required oxygen, glucose, and other substances, while preventing harmful substances, pathogens, and other potentially harmful substances from entering the brain. Once the expression or function of Claudin-5 becomes abnormal, the function of BBB will be affected, thus triggering a series of nervous system diseases, such as neuroinflammation, cerebrovascular disease and neurodegenerative diseases. Epilepsy is a disease caused by abnormal neural discharges. Some studies have shown that Claudin-5 may be involved in the pathogenesis of epilepsy by changing the permeability of the BBB and affecting the ion concentration in the brain tissue. Although the specific mechanism is not fully understood at present, changes in Claudin-5 may be closely related to the occurrence of epilepsy. In summary, Claudin-5 not only plays a vital role in maintaining the integrity of the BBB, but also has potential research value in the pathogenesis of central nervous system diseases, especially epilepsy. This article will review the physiological functions, pathological changes, and role of Claudin-5 in maintaining BBB integrity and epilepsy, providing new ideas for the treatment of epilepsy.
- Epilepsy /
- Blood-brain barrier /
- Tight junctions /
- Claudin-5

HTML全文

图 1 血脑屏障结构及破坏示意图

注：A为星形胶质细胞，B为神经元，C为基底膜，D为周细胞，E为紧密连接，F为内皮细胞，G为钾离子，H为白细胞。

Figure 1. Schematic diagram of the blood-brain barrier structure and its disruption

下载: 全尺寸图片幻灯片

图 2 Claudin结构示意图

注：Claudin家族是存在于上皮和内皮间顶端的膜蛋白，作为四次跨膜蛋白家族，包含27个成员。有4个跨膜结构域，包括位于细胞质中的N端和C端，以及2个胞外结构域。A为细胞外环-1；B为细胞外环-2；C为NH2-端；D为COOH-端；E为细胞膜。

Figure 2. Schematic diagram of Claudin structure

下载: 全尺寸图片幻灯片

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