肠道大麻素受体1调节酒精过度饮酒引起的肠道透性
Luca Maccioni1,2, Szabolcs Dvorácskó2,3,4,5, Grzegorz Godlewski2
1Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA.
eGastroenterology
|March 24, 2025
概括
过度饮酒会通过激活肠道上皮类大麻素受体1 (CB1R) 来增加肠道的通透性. 用抗体准CB1R可以防止这种酒精诱导的漏肠,改善肠道屏障功能.
科学领域:
- 胃肠病学 胃肠病学
- 药理学 药理学是指药理学的学科.
- 内分泌学 在内分泌学.
背景情况:
- 众所周知,通过大麻素受体1 (CB1R) 作用的内分类固醇可以增加肠道的通透性.
- 过度饮酒会对消化功能产生负面影响,包括肠道透性,但机制尚未完全理解.
研究的目的:
- 调查CB1R在酒精过度饮酒引起的肠透性中的作用.
- 为了确定是否准肠上皮的CB1R可以防止酒精诱导的漏肠.
主要方法:
- 开发了肠道表皮特异性的CB1R淘汰 (CB1IEC-/-) 鼠标.
- 给出了外围CB1R抗剂,以评估其对野生类型和淘汰赛小鼠酒精过度诱导肠道透性的影响.
- 评估了肠道透性,紧结蛋白表达和小长度.
主要成果:
- 酒精过度饮酒增加了肠道透性和近端小肠中的安纳米德水平.
- 肠道CB1R的遗传删除防止了酒精诱导的肠道透性的增加.
- 一种外围CB1R抗剂在对照小鼠中降低了酒精诱导的肠道透性,但在CB1IEC-/-小鼠中没有.
- 酒精激活了肠上皮 CB1R-ERK1/2 途径,导致紧接口蛋白降低调节和减少小长度,在准 CB1R 和 ERK1/2.2 后可逆.
结论:
- 过度饮酒会通过激活肠道上皮细胞CB1R.促进"漏肠".
- 局限于外围的选择性CB1R抗剂可以防止酒精过度饮酒引起的肠透性,从而改善肠道屏障功能.
关键词:
胃肠道疾病 胃肠道疾病更多相关视频
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