College of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, No. 37, 12 Bridge Road, Chengdu 610075, PR China.
Integrative Medical Center, The Fifth Medical Center of PLA General Hospital, Beijing 100039, PR China.
Life Sci. 2020 May 1;248:117456. doi: 10.1016/j.lfs.2020.117456. Epub 2020 Feb 22.
In this study, we will investigate the therapeutic effects of berberine (BBR) in Helicobacter pylori (H. pylori) induced chronic atrophic gastritis (CAG). Furthermore, potential mechanisms of BBR in regulating IRF8-IFN-γ signaling axis will also be investigated.
H. pylori were utilized to establish CAG model of rats. Therapeutic effects of BBR on serum supernatant indices, and histopathology of stomach were analyzed in vivo. Moreover, GES-1 cells were infected by H. pylori, and intervened with BBR in vitro. Cell viability, morphology, proliferation, and quantitative analysis were detected by high-content screening (HCS) imaging assay. To further investigate the potential mechanisms of BBR, relative mRNA, immunohistochemistry and protein expression in IRF8-IFN-γ signaling axis were measured.
Results showed serum supernatant indices including IL-17, CXCL1, and CXCL9 were downregulated by BBR intervention, while, G-17 increased significantly. Histological injuries of gastric mucosa induced by H. pylori also were alleviated. Moreover, cell viability and morphology changes of GES-1 cells were improved by BBR intervention. In addition, proinflammatory genes and IRF8-IFN-γ signaling axis related genes, including Ifit3, Upp1, USP18, Nlrc5, were suppressed by BBR administration in vitro and in vivo. The proteins expression related to IRF8-IFN-γ signaling axis, including Ifit3, IRF1 and Ifit1 were downregulated by BBR intervention.
本研究旨在探讨小檗碱（BBR）在幽门螺杆菌（H. pylori）诱导的慢性萎缩性胃炎（CAG）中的治疗作用。此外，还将研究 BBR 调节 IRF8-IFN-γ 信号轴的潜在机制。
利用 H. pylori 建立大鼠 CAG 模型，分析 BBR 对血清上清指标和胃组织病理学的体内治疗作用。此外，体外将 GES-1 细胞感染 H. pylori ，并用 BBR 干预。通过高内涵筛选（HCS）成像检测细胞活力、形态、增殖和定量分析。为进一步探讨 BBR 的潜在机制，测量了 IRF8-IFN-γ 信号轴相关的相对 mRNA、免疫组织化学和蛋白表达。
结果表明，BBR 干预可下调血清上清液中包括 IL-17、CXCL1 和 CXCL9 在内的指标，而 G-17 则显著增加。H. pylori 诱导的胃黏膜组织学损伤也得到缓解。此外，BBR 干预可改善 GES-1 细胞的活力和形态变化。此外，BBR 体内外给药可抑制促炎基因和 IRF8-IFN-γ 信号轴相关基因，包括 Ifit3、Upp1、USP18、Nlrc5。IRF8-IFN-γ 信号轴相关蛋白表达，包括 Ifit3、IRF1 和 Ifit1 ，也被 BBR 下调。
