College of Animal Science, Zhejiang University, Key Laboratory of Animal Nutrition & Feed Sciences, Ministry of Agriculture , Zhejiang Provincial Laboratory of Feed and Animal Nutrition , No. 866 Yuhangtang Road , Hangzhou , Zhejiang 310058 , P. R. China.
Mol Pharm. 2018 Aug 6;15(8):3272-3284. doi: 10.1021/acs.molpharmaceut.8b00332. Epub 2018 Jul 13.
Metformin not only regulates energy metabolism but also participates in many cellular processes. In this study, we investigated the effect of metformin on lipopolysaccharide (LPS)-induced intestinal barrier damage. We found that LPS treatment decreased the expression of tight junction proteins and caused a proinflammatory response and oxidative stress in the intestine. Interestingly, metformin treatments attenuated LPS-induced intestinal barrier damage, inflammation, and oxidative stress. We found that metformin improved the expression of intestinal tight junction proteins (ZO1, occludin, and Claudin1) that were reduced by LPS stimulation. Moreover, metformin alleviated LPS-induced NF-κB phosphorylation, promoted Nrf2 nuclear translocation, and increased the expression of the antioxidative genes (HO-1 and NQO-1), leading to reduced intestinal ROS content. Mechanistically, we found that metformin protects against LPS-induced intestinal barrier dysfunction by activating AMPK. These results reveal the potential of metformin as an effective therapy for treating intestinal diseases.
二甲双胍不仅调节能量代谢，还参与许多细胞过程。在这项研究中，我们研究了二甲双胍对脂多糖（LPS）诱导的肠道屏障损伤的影响。我们发现，LPS 处理降低了紧密连接蛋白的表达，并导致肠道发生炎症反应和氧化应激。有趣的是，二甲双胍治疗可减轻 LPS 诱导的肠道屏障损伤、炎症和氧化应激。我们发现，二甲双胍改善了 LPS 刺激减少的肠道紧密连接蛋白（ZO1、occludin 和 Claudin1）的表达。此外，二甲双胍减轻了 LPS 诱导的 NF-κB 磷酸化，促进了 Nrf2 核易位，并增加了抗氧化基因（HO-1 和 NQO-1）的表达，从而减少了肠道 ROS 含量。在机制上，我们发现二甲双胍通过激活 AMPK 来防止 LPS 诱导的肠道屏障功能障碍。这些结果揭示了二甲双胍作为治疗肠道疾病的有效疗法的潜力。
