西格玛-1受体激活通过抑制内分泌网膜压力依赖自来缓解I/R损伤后的IBRB功能障碍
Jian Yu1,2, Jiaojiao Wei1,2, Yuan Zong1,2
1Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, 200031, China.
Molecular neurobiology
|June 1, 2025
概括
激活西格玛-1受体 (σ1R) 通过减少ER压力和自来保护受伤后的内血液视网膜屏障. 这种机制保留了紧结蛋白和内皮功能,提供了潜在的治疗点.
科学领域:
- 眼科医生 眼科 眼科
- 神经科学是一个神经科学.
- 细胞生物学 细胞生物学
背景情况:
- 视网膜缺血/反 (I/R) 损伤损害了内部血液-视网膜屏障 (iBRB).
- 西格玛-1受体 (σ1R) 与细胞应激反应有关.
- 了解 σ1R 在iBRB 保护中的作用对于开发治疗方法至关重要.
研究的目的:
- 为了研究 σ1R 激活在视网膜 I/R 损伤后对iBRB 的保护作用.
- 阐明涉及ER应激,自和紧密结合蛋白的潜在分子机制.
主要方法:
- 建立了视网膜I/R损伤的小鼠模型和体外氧气-葡萄糖剥夺/再输液 (OGD/R) 细胞模型.
- 用于体内和体外实验的 σ1R 激活剂 (SA4503) 和对抗剂 (BD1047).
- 评估了iBRB完整性,紧结蛋白表达,ER压力标志物和自流量,使用西方抹杀,免疫光和基于细胞的测试.
主要成果:
- 用SA4503激活s1R显著减少了血管泄漏,并在I/R受伤的视网膜中保留了紧接口蛋白.
- 治疗SA4503减弱了内质网膜 (ER) 的压力和抑制了自.
- 抑制ER应激或自途径抵消了SA4503的保护作用,表明它们参与了该机制.
结论:
- σ1R激活对I/R损伤后的iBRB和视网膜毛细体内皮功能产生显著的保护作用.
- 保护机制涉及抑制ER应力依赖的自和随后的紧密结合蛋白的保存.
- 准 σ1R 是一个有前途的治疗策略,用于管理视网膜 I/R 损伤.
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