酒精诱导的肠道透性缺陷通过失生症和肠细胞线粒体干扰引起亲炎性巨细胞以剂量依赖的方式
Wiwat Chancharoenthana1,2, Supitcha Kamolratanakul3,4, Kanyarat Udompornpitak5,6
1Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, 16/F Ratchanakarin Building 420/6 Rajvithi Rd., Ratchathewi, Bangkok, 10400, Thailand. wiwat.cha@mahidol.ac.th.
低剂量和高剂量的酒精都会导致小鼠的肠道泄漏. 高剂量的酒精还会导致肠道失调和肝损伤,表明剂量依赖的肠道损伤.
科学领域:
- 胃肠病学 胃肠病学
- 毒理学 毒理学 毒理学
- 免疫学 免疫学 免疫学
背景情况:
- 饮酒与肠道和免疫系统的毒性有关.
- 低剂量与高剂量酒精对肠道的差异性影响尚未完全理解.
- 在SHIRPA等简单的评分系统的帮助下,动物模型对于研究酒精影响非常有价值.
研究的目的:
- 在动物模型中调查低剂量和高剂量酒精管理对肠道完整性,肠道微生物群和肝脏健康的明显影响.
- 评估SHIRPA得分与酒精剂量和观察到的生理变化相关的有用性.
主要方法:
- 在16周的时间里,小鼠接受了低剂量 (6.30g/kg/天) 或高剂量 (1.26g/kg/天) 的酒精.
- 血中酒精度 (BAC) 和SHIRPA得分在药物后被记录下来.
- 肝脏酶,肝脏重量,组织学,亡,甘油三 (TG),甲酸 (MDA) 和谷氨水平进行了评估.
- 通过使用FITC-dextran,内毒素,血清β-葡萄糖和奥克卢丁水平来评估肠道透性.
- 进行了便微生物组分析.
主要成果:
- 高剂量的酒精显著增加了肝酶,肝脏重量,亡,TG和MDA,同时减少了谷氨.
- 低剂量的酒精增加了肝脏中的亡,TG和MDA.
- 这两种剂量都诱导了肠道泄漏,由增加的FITC-dextran,内毒素,β-葡萄糖和减少的奥克卢丁证明.
- 高剂量的酒精改变了肠道微生物组合 (增加了Alitipes,减少了Lachnospiraceae),与低剂量不同.
- 酒精损害了线粒体,但增强了肠细胞和巨细胞的葡萄糖分解.
结论:
- 低剂量和高剂量的酒精都会诱导肠道屏障功能障碍 (漏肠).
- 高剂量的酒精会导致严重的肝损伤和肠道失调,而低剂量的酒精会显示出较轻微的肝脏影响.
- 漏肠似乎是一个更敏感的指标酒精诱导的肠道损伤比肠道失调.
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