Gastric ulcer (GU) is one of the most common diseases of the upper gastrointestinal tract that affects millions of people worldwide. This study aimed to investigate the possible alleviating effect of a combined treatment of pantoprazole (PANTO) and adipose tissue-derived mesenchymal stem cells (ADSCs) in comparison with each treatment alone on the healing process of the experimentally induced GU in rats, and to uncover the involved pathways. Rats were divided into five groups: (1) Control, (2) GU, (3) PANTO, (4) ADSCs and (5) ADSCs + PANTO. Markers of oxidative stress, inflammation and apoptosis were assessed. The current data indicated that PANTO-, ADSCs- and ADSCs + PANTO-treated groups showed significant drop (p < 0.05) in serum advanced oxidation protein products (AOPPs) and advanced glycation end products (AGEPs) along with significant elevation (p < 0.05) in serum TAC versus the untreated GU group. Moreover, the treated groups (PANTO, ADSCs and ADSCs + PANTO) displayed significant down-regulation (p < 0.05) in gastric nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), tumor necrosis factor alpha (TNF-α), cyclooxygenase-2 (COX-2), intercellular adhesion molecule-1 (ICAM-1), matrix metallopeptidase 9 (MMP-9) and caspase-3 along with significant up-regulation (p < 0.05) in vascular endothelial growth factor (VEGF) and peroxisome proliferator-activated receptor gamma (PPARγ) genes expression compared to the untreated GU group. Immunohistochemical examination of gastric tissue for transforming growth factor β1 (TGF-β1), epidermal growth factor (EGF) and proliferating cell nuclear antigen (PCNA) showed moderate to mild and weak immune reactions, respectively in the PANTO-, ADSCs- and ADSCs + PANTO-treated rat. Histopathological investigation of gastric tissue revealed moderate to slight histopathological alterations and almost normal histological features of the epithelial cells, gastric mucosal layer, muscularis mucosa and submucosa in PANTO-, ADSCs- and ADSCs + PANTO-treated rats, respectively. Conclusively, the co-treatment with ADSCs and PANTO evidenced sententious physiological protection against GU by suppressing oxidative stress, inhibiting inflammation and reducing apoptosis with consequent acceleration of gastric tissue healing process.

胃溃疡（GU）是上消化道最常见的疾病之一，影响着全世界数百万人。本研究旨在探讨泮托拉唑 (PANTO) 和脂肪组织源性间充质干细胞 (ADSC) 联合治疗与单独治疗相比对实验诱导的 GU 愈合过程的可能缓解作用，并揭示所涉及的途径。将大鼠分为五组：(1)对照组、(2)GU、(3)PANTO、(4)ADSC和(5)ADSC+PANTO。评估了氧化应激、炎症和细胞凋亡的标志物。当前数据表明，PANTO-、ADSC- 和 ADSC+PANTO 治疗组的血清高级氧化蛋白产物 (AOPP) 和晚期糖基化终末产物 (AGEP) 显着下降 ( p  <  0.05 )，同时显着升高 ( p  <  0.05) ) 血清 TAC与未治疗 GU 组相比。此外，治疗组（PANTO、ADSC 和 ADSC + PANTO）显示胃核因子 kappa 激活 B 细胞轻链增强子（NF-κB）、肿瘤坏死因子 α（ p < 0.05 ）显着下调（p  <  0.05）。 TNF-α)、环氧合酶-2 (COX-2)、细胞间粘附分子-1 (ICAM-1)、基质金属肽酶 9 (MMP - 9) 和 caspase-3 以及血管中的显着上调 ( p  <  0.05 )与未治疗的 GU 组相比，内皮生长因子 (VEGF) 和过氧化物酶体增殖物激活受体 γ (PPARγ) 基因表达。胃组织转化生长因子β1（TGF-β1）、表皮生长因子（EGF）和增殖细胞核抗原（PCNA）的免疫组织化学检查分别在PANTO-、ADSC-和ADSC+中显示中度至轻度和弱免疫反应PANTO 处理的大鼠。胃组织的组织病理学研究显示，PANTO-、ADSC-和ADSC+PANTO处理的大鼠的上皮细胞、胃粘膜层、粘膜肌层和粘膜下层分别有中度至轻微的组织病理学改变和几乎正常的组织学特征。总之，ADSC 和 PANTO 联合治疗通过抑制氧化应激、抑制炎症和减少细胞凋亡，从而加速胃组织愈合过程，证明对 GU 具有显着的生理保护作用。