Department of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China; Department of Infectious Diseases, Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Department of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Nutrition. 2022 Jul-Aug;99-100:111673. doi: 10.1016/j.nut.2022.111673. Epub 2022 Apr 1.
We aimed to explore whether Lactobacillus reuteri could have a positive role in reducing inflammation and bacterial translocation in rats with acute liver failure.
Lactobacillus reuteri were gavaged to Sprague-Dawley (SD) rats at a dose of 1 × 10 CFU/mL once a day for 14 d. D-galactosamine was injected intraperitoneally to induce acute liver failure for 24 h on the 15th day. Liver function, liver and ileum histology, intestinal cytokines, intestinal tight junction proteins, lipopolysaccharide binding protein, apoptosis molecules, and nuclear factor erythroid-derived 2 (Nrf-2) / heme oxygenase (HO-1) molecules were assessed.
The results showed that L. reuteri alleviated liver injury and intestinal inflammation induced by D-galactosamine. L. reuteri also improved the expression of intestinal tight junction proteins and maintained the integrity of the intestinal barrier by inhibiting apoptosis of intestinal epithelial cells. L reuteri induced an increase in Nrf-2 nuclear translocation and elevated induction of HO-1. L. reuteri treatment significantly enhanced the expression of phosphoinositide 3-kinase/protein kinase B (PI3 K/Akt), protein kinase C (PKC), and their phosphorylated forms but not mitogen-activated protein kinase. The nuclear factor kappa B (NF-κB) pathway was inhibited after L. reuteri treatment. Interleukin (IL)-17A produced by Th17 cells and γδT17 cells may not contribute to an improved function of the intestinal barrier in L. reuteri-treated SD rats.
Overall, our study indicated that L. reuteri-induced expression of intestinal tight junction proteins is mediated by the PI3 K/Akt-Nrf-2/HO-1-NF-κB and PKC-Nrf-2/HO-1-NF-κB pathways, which leads to inhibition of the apoptosis of intestinal epithelial cells, thus maintaining the integrity of the damaged intestinal barrier.
本研究旨在探讨罗伊氏乳杆菌是否能在急性肝衰竭大鼠中发挥减轻炎症和细菌易位的积极作用。
采用腹腔注射半乳糖胺（D-galactosamine，D-gal）的方法复制大鼠急性肝衰竭模型，15 日龄时大鼠一次性腹腔注射 D-gal 200mg/kg 复制急性肝衰竭模型，14 日龄时每日经口灌胃罗伊氏乳杆菌（Lactobacillus reuteri）1×10CFU/ml 一次，连续 14 天。检测各组大鼠肝功能、肝组织和回肠组织病理学变化、肠道细胞因子、紧密连接蛋白、内毒素结合蛋白（lipopolysaccharide binding protein，LBP）、凋亡相关蛋白、核因子红细胞衍生 2（nuclear factor erythroid 2，Nrf-2）/血红素加氧酶 1（heme oxygenase 1，HO-1）通路相关蛋白。
L. reuteri 减轻了 D-gal 诱导的大鼠肝损伤和肠道炎症。L. reuteri 还通过抑制肠上皮细胞凋亡，改善了肠道紧密连接蛋白的表达，维持了肠道屏障的完整性。L. reuteri 诱导 Nrf-2 核易位增加，HO-1 诱导增加。L. reuteri 治疗显著增强了磷酸肌醇 3-激酶/蛋白激酶 B（phosphoinositide 3-kinase/protein kinase B，PI3 K/Akt）、蛋白激酶 C（protein kinase C，PKC）及其磷酸化形式的表达，但不影响丝裂原活化蛋白激酶（mitogen-activated protein kinase，MAPK）。L. reuteri 处理后抑制了核因子 kappa B（nuclear factor kappa B，NF-κB）通路。Th17 细胞和γδT17 细胞产生的白细胞介素（interleukin，IL）-17A 可能不会促进 L. reuteri 处理的 SD 大鼠肠道屏障功能的改善。
综上所述，本研究表明，L. reuteri 诱导的肠道紧密连接蛋白表达是通过 PI3 K/Akt-Nrf-2/HO-1-NF-κB 和 PKC-Nrf-2/HO-1-NF-κB 途径介导的，该途径抑制了肠上皮细胞的凋亡，从而维持了受损肠道屏障的完整性。
