由肠道微生物群产生的烯酸减轻了乙胺诱导的肝毒性
Sungjoon Cho1, Xiaotong Yang1, Kyoung-Jae Won1,2
1Department of Pharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA.
Gut microbes
|July 11, 2023
概括
一种肠道细菌代谢物,酸 (PPA),控制肝脏酶CYP2E1,影响乙氨基的毒性. 补充PPA可以通过降低CYP2E1水平来防止肝损伤.
科学领域:
- 微生物学 微生物学
- 肝病学 肝病学是一种肝病学.
- 药理学 药理学是指药理学的学科.
背景情况:
- 肠道微生物群显著影响肝脏药物代谢,但特定的微生物因素在很大程度上仍未确定.
- 过量服用乙氨基 (APAP) 会导致肝损伤,部分由肝酶CYP2E1调解,该酶将APAP转化为有毒代谢物.
研究的目的:
- 确定调节肝脏药物代谢并影响乙氨基诱导的肝毒性肠道微生物因素.
- 调查烯酸 (PPA) 在调节CYP2E1表达中的作用及其对肝损伤的影响.
主要方法:
- 在C57BL/6亚菌株小鼠 (杰克逊和塔科尼克) 与明显的肠道微生物群中比较乙氨基诱导的肝毒性.
- 在没有细菌的小鼠身上进行微生物群移植实验,以确认肠道微生物群的作用.
- 对血清和肝脏组织进行非向的代谢分析,以确定关键代谢物.
- 在肝损伤的小鼠模型中,用酸 (PPA) 进行补充研究.
主要成果:
- 在小鼠供应商之间肠道微生物群的差异与对APAP诱导的肝毒性有不同的敏感性相关.
- 烯酸 (PPA) 被确定为一种代谢物,在不太敏感的小鼠中存在更高的水平.
- 通过降低肝脏CYP2E1度,PPA补充剂减少了APAP诱导的肝毒性和四化碳诱导的肝损伤.
- 实验室研究表明,虽然两种小鼠肠道微生物都能产生PPA,但其体内生产在一个组中被抑制,这表明未识别的微生物参与其中.
结论:
- 肠道细菌代谢物烯酸 (PPA) 通过调节肝脏CYP2E1表达在肠-肝脏轴上发挥关键作用.
- PPA对乙氨基和四化碳引起的肝损伤具有保护作用.
- 这些发现突出了PPA作为管理CYP2E1介导性肝病和代谢障碍的潜在治疗点.
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