Qi Zhu, Jie Li, Haixia Cao, Xiaoying Zhao
Department of Gastroenterology, Shanghai Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.
Dig Dis Sci. 2009 Sep;54(9):1876-83. doi: 10.1007/s10620-008-0577-3. Epub 2008 Dec 11.
The aim of this study is to elucidate the effects and the mechanism of rebamipide, omeprazole, and their combination treatment on quality of peptic ulcer healing (QOUH). Peptic ulcer models were induced by acetic acid exposure of the serosa of rat stomach. Forty Sprague-Dawley (SD) rats were divided randomly into four groups of ten rats each. Saline 2 ml/d (group 1), rebamipide 60 mg/kg/d (group 2), omeprazole 10 mg/kg/d (group 3) as well as its combination regimen (group 4) were administrated for 7 days. After sacrifice, size of the ulcer and focal layer structures were measured in vitro by miniature ultrasonic probe, and the mucosal sections were stained with hematoxylin and eosin (HE) for histological examination; the levels of interleukin (IL)-8/prostaglandin E(2) (PGE(2)) were evaluated by enzyme-linked immunosorbent assay (ELISA) and malondialdehyde (MDA) level was evaluated by thiobarbituric acid (TBA) method. Macroscopically, compared with the control group, the maximal diameters of the ulcers in the medication groups were significantly reduced (P < 0.05), and the layer echo structures of gastric wall were partially rebuilt. Histologically, ulcer range and inflammatory infiltration were less severe compared with the control group. In addition, mucosal MDA and IL-8 levels were significantly decreased, while PGE(2) level was significantly increased in the medication groups. Between the two monotherapy groups, there was no statistical difference in terms of PGE(2) and MDA levels. However, PGE(2) level was significantly increased, while MDA and IL-8 levels were significantly decreased in the combination group. Rebamipide as well as omeprazole and the combination regimen may improve QOUH through increasing the level of PGE(2), decreasing the levels of IL-8 and MDA in gastric mucosa, and this may potentially result in reduced recurrence of ulcer; moreover, the combination regimen was identified as having more antiulcer effects than monotherapy.
本研究旨在阐明瑞巴派特、奥美拉唑及其联合治疗对消化性溃疡愈合质量（QOUH）的影响及机制。通过大鼠胃浆膜醋酸暴露诱导消化性溃疡模型。40只Sprague-Dawley（SD）大鼠随机分为四组，每组10只。分别给予2 ml/d生理盐水（第1组）、60 mg/kg/d瑞巴派特（第2组）、10 mg/kg/d奥美拉唑（第3组）及其联合用药方案（第4组），给药7天。处死后，用微型超声探头在体外测量溃疡大小和局部层结构，并用苏木精和伊红（HE）对黏膜切片进行染色以进行组织学检查；采用酶联免疫吸附测定（ELISA）评估白细胞介素（IL）-8/前列腺素E2（PGE2）水平，采用硫代巴比妥酸（TBA）法评估丙二醛（MDA）水平。宏观上，与对照组相比，用药组溃疡的最大直径显著减小（P<0.05），胃壁层回声结构部分重建。组织学上，与对照组相比，溃疡范围和炎症浸润较轻。此外，用药组黏膜MDA和IL-8水平显著降低，而PGE2水平显著升高。在两个单药治疗组之间，PGE2和MDA水平无统计学差异。然而，联合组PGE2水平显著升高，而MDA和IL-8水平显著降低。瑞巴派特以及奥美拉唑及其联合用药方案可能通过提高PGE2水平、降低胃黏膜中IL-8和MDA水平来改善QOUH，这可能会降低溃疡复发率；此外，联合用药方案被证实比单药治疗具有更强的抗溃疡作用。
