阻断TRPM4可以通过一种依赖NMDA受体的途径缓解胰腺状细胞损伤,这种途径可用于急性胰腺炎
Yifan Ren1,2, Qing Cui3, Wuming Liu1,4
1National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi'an Jiaotong University. Xi'an, Shaanxi Province, China.
Theranostics
|June 30, 2025
概括
短暂的受体潜在阴阳通道 melastatin 4 (TRPM4) 的激活会通过损害线粒体功能而加剧急性胰腺炎 (AP). 针对TRPM4/NMDARs途径为AP提供了一个新的治疗策略.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 病理生理学 病理生理学
背景情况:
- 胰腺细胞中过载导致的线粒体功能障碍是急性胰腺炎 (AP) 发病的关键.
- 暂时受体潜在阴离子通道 melastatin 4 (TRPM4) 与神经元线粒体损伤有关,但其在 AP 中的作用尚不清楚.
研究的目的:
- 调查TRPM4激活在急性胰腺炎期间线粒体功能障碍和细胞死亡中的作用.
- 在AP中探索针对TRPM4的治疗潜力.
主要方法:
- 使用了AP (L-氨酸,氨酸+LPS,仅氨酸) 和AR42J细胞的小鼠模型.
- 使用的基因淘汰/缺陷 (Trpm4) 和TRPM4.的药理抑制 (9-phenanthrol).
- 研究了N-甲基-D-酸盐受体 (NMDARs) 在TRPM4-介导的AP病变发生过程中的参与.
主要成果:
- 在AP模型中,胰腺TRPM4水平增加.
- 在AP小鼠中,TRPM4抑制或缺乏改善了胰腺损伤和降低了死亡率.
- 抑制TRPM4改善了线粒体功能,并与NMDARs相关,减轻了ER压力和细胞死亡.
结论:
- 通过一种依赖NMDAR的途径,TRPM4的激活有助于AP中的胰腺状细胞损伤.
- TRPM4/NMDARs复合体为急性胰腺炎提供了一个新的治疗点.
相关概念视频
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Pancreatitis is inflammation of the pancreas, an organ located behind the stomach. It can be either acute or chronic.
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