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滑动肌肉对胆酸的收缩反应需要TGR5,但不需要ASBT
Diana S Chang1, Krishnakant G Soni1, Geoffrey A Preidis1
1Division of Gastroenterology, Hepatology & Nutrition, Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, TX, United States.
Frontiers in neurology
|May 9, 2024
概括
胆汁酸通过TGR5信号传递对肠道运动有不同的影响,独立于性别或ASBT. 乌尔苏多氧胆酸 (UDCA) 增加了收缩性,而脱氧胆酸 (DCA) 没有. 这揭示了治疗肠-大脑相互作用障碍的机制.
科学领域:
- 胃肠病学 胃肠病学
- 生理学 生理学 生理学
- 药理学 药理学是指药理学的学科.
背景情况:
- 肠-大脑相互作用障碍 (DGBIs) 在女性中更为常见,涉及肠道运动和胆酸平衡的改变.
- 连接胆汁酸与胃肠机动性的机制尚不清楚.
- 之前的研究表明,对乌尔索德氧化胆酸 (UDCA) 和脱氧化胆酸 (DCA) 的阴茎收缩反应不同.
研究的目的:
- 调查胆酸诱导的胆管收缩反应是否取决于宿主性别,TGR5或ASBT.
- 阐明参与胆汁酸调节肠道运动的信号通路.
主要方法:
- 在组织浴实验中使用了转移的小鼠叶片段.
- 对UDCA和DCA的收缩反应与TGR5或ASBT抑制剂或没有TGR5或ASBT抑制剂一起测量.
- 西方涂抹评估了ERK和MLC的酸化,作为TGR5激活和光滑肌肉收缩的标记.
主要成果:
- 在胆酸诱导的胆管收缩性中没有观察到性别差异.
- UDCA,但不是DCA,在100μmol/L时增加了MLC的酸化和收缩性.
- 抑制TGR5降低了ERK和MLC的酸化,收缩性,甚至降低了MLC总水平.
- 抑制ASBT对收缩反应没有影响.
结论:
- 关于UDCA和DCA对以利亚平滑肌收缩性的不同影响是独立于性别和ASBT的.
- 胆酸通过粘膜TGR5发出信号,通过复杂的机制调节光滑肌肉收缩性.
- 了解这些机制可能会导致DGBIs的新疗法.
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