Department of Physiology, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.
Department of Anesthesiology and Pain Medicine, Kyung Hee Medical Center, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.
Life Sci. 2018 Jun 15;203:12-19. doi: 10.1016/j.lfs.2018.04.009. Epub 2018 Apr 14.
The main action of proton pump inhibitors (PPIs) is to inhibit gastric acid secretion, and PPIs are widely used to treat gastric ulcer (GU). However, if the action of promoting gastric mucosal regeneration is added, the effectiveness of GU treatment can be enhanced. Thus, in order to improve the therapeutic effect on GU, we tried to develop combination therapy promoting regeneration in injured tissue besides suppressing gastric acid secretion.
Polydeoxyribonucleotide (PDRN) was selected to evaluate tissue regeneration, and pantoprazole was chosen as one of the PPIs. GU was induced by oral administration of indomethacin once a day for 7 days. Rats in drug-administered groups were intraperitoneally injected with 100 μL normal saline, containing each drug at the indicated concentration, once a day for 14 days after inducing GU.
PDRN and PPI combination therapy potently improved tissue regeneration and inhibited production of pro-inflammatory cytokines. PDRN treatment with or without PPI increased the concentration of cyclic adenosine-3,5'-monophosphate (cAMP) and the ratio of phosphorylated cAMP response element-binding protein (p-CREB) to cAMP response element-binding protein (CREB). PDRN treatment with or without PPI also increased the expressions of vascular endothelial growth factor (VEGF) and adenosine A receptor.
PDRN and PPI combination therapy showed more potent therapeutic effect on GU compared to the PDRN monotherapy or PPI monotherapy. The excellent therapeutic effect of PDRN and PPI combination therapy on GU appeared by promoting regeneration of damaged tissue as well as inhibiting gastric acid secretion.
质子泵抑制剂（PPIs）的主要作用是抑制胃酸分泌，广泛用于治疗胃溃疡（GU）。然而，如果加入促进胃黏膜再生的作用，GU 的治疗效果可以增强。因此，为了提高 GU 的治疗效果，我们试图在抑制胃酸分泌的基础上开发促进损伤组织再生的联合治疗方法。
选择聚脱氧核糖核苷酸（PDRN）来评估组织再生，选择泮托拉唑作为 PPI 之一。通过每天口服吲哚美辛一次诱导 GU，持续 7 天。在药物治疗组中，在诱导 GU 后第 14 天，每天腹腔注射 100 μL 生理盐水，其中含有每种药物的指定浓度。
PDRN 和 PPI 联合治疗可显著促进组织再生并抑制促炎细胞因子的产生。单独使用 PDRN 或联合 PPI 治疗均可增加环腺苷酸-3'，5'-单磷酸（cAMP）的浓度和磷酸化 cAMP 反应元件结合蛋白（p-CREB）与 cAMP 反应元件结合蛋白（CREB）的比值。单独使用 PDRN 或联合 PPI 治疗还可增加血管内皮生长因子（VEGF）和腺苷 A 受体的表达。
与 PDRN 单药治疗或 PPI 单药治疗相比，PDRN 和 PPI 联合治疗对 GU 具有更强的治疗效果。PDRN 和 PPI 联合治疗对 GU 的优异治疗效果通过促进损伤组织的再生以及抑制胃酸分泌来实现。
