The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China; Department of Gastroenterology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
Department of Pharmacy, Zhuhai Center for Maternal and Child Health Care, Zhuhai, China.
Biomed Pharmacother. 2020 Oct;130:110472. doi: 10.1016/j.biopha.2020.110472. Epub 2020 Jul 29.
De novo lipogenesis (DNL) has been reported to involve in a serial types of disease. A standard triple therapy, including a PPI, omeprazole, and antibiotics (clarithromycin and amoxicillin), is widely used as the first-line regimen for helicobacter pylori (H. pylori)-infectious treatment. The objective of this study is to explore the function of a standard triple therapy on DNL.
We collected the clinical sample from the patients diagnosed with or without H. pylori infection. Oil red staining, real-time PCR, western blotting (WB) and adipored experiment were performed to detect the effect of a standard triple therapy on DNL. The expression of relative key enzymes was assessed in gastric mucosa of clinical sample by IHC. Both 54 cases with H. pylori-negative and 37 cases with H. pylori-positive were enrolled in this study, and IHC assay showed that both fatty acid synthase (FASN) and ATP-citrate lyase (ACLY) expression, the critical enzymes involved in DNL, were increased in gastric mucosa of patients with H. pylori-positive compared with that with H. pylori-negative. Real-time PCR and WB analysis showed that neither clarithromycin nor amoxicillin inhibited FASN and ACLY expression, while treatment of BGC823 cells with omeprazole with 200 μM or 300 μM significantly abolished FASN and ACLY expression, leading to reduce lipid content.
These findings suggested that omeprazole suppressed DNL in gastric cells, implying that targeting DNL is an alternative strategy in improving the treatment of patients with H. pylori infection.
从头合成脂肪（DNL）已被报道与一系列疾病有关。质子泵抑制剂（PPI）、奥美拉唑和抗生素（克拉霉素和阿莫西林）三联疗法被广泛用作幽门螺杆菌（H. pylori）感染治疗的一线方案。本研究旨在探讨标准三联疗法对 DNL 的作用。
我们收集了诊断为 H. pylori 感染或未感染的患者的临床样本。通过油红染色、实时 PCR、western blot（WB）和脂肪生成实验检测标准三联疗法对 DNL 的影响。通过免疫组织化学评估临床样本胃黏膜中相对关键酶的表达。本研究共纳入 54 例 H. pylori 阴性和 37 例 H. pylori 阳性患者，免疫组化检测显示，H. pylori 阳性患者胃黏膜中脂肪酸合酶（FASN）和三磷酸柠檬酸裂解酶（ACLY）的表达均高于 H. pylori 阴性患者，这两种酶均参与 DNL。实时 PCR 和 WB 分析表明，克拉霉素和阿莫西林均不能抑制 FASN 和 ACLY 的表达，而奥美拉唑 200 μM 或 300 μM 处理 BGC823 细胞可显著抑制 FASN 和 ACLY 的表达，导致脂质含量减少。
这些发现表明，奥美拉唑抑制胃细胞中的 DNL，提示靶向 DNL 是改善 H. pylori 感染患者治疗的一种替代策略。
