Udagawa A, Shiota G, Ichiba M, Murawaki Y
Second Dept. of Internal Medicine, Faculty of Medicine, Tottori University, Yonago, Japan.
Scand J Gastroenterol. 2003 Feb;38(2):141-6. doi: 10.1080/00365520310000609.
Rebamipide is used clinically as an anti-ulcer agent, especially in Japan. The major mechanisms of rebamipide include prostaglandin induction and free radical scavenging. Since prostaglandins are inducers of hepatocyte growth factor (HGF), we examined the effect of rebamipide on the expression of HGF, c-met, cyclooxygenase-2 (Cox-2) and subtype of the prostaglandin E2 receptor (EP2) in acetic acid-induced gastric ulcer, a model of human ulcer.
Ninety-six male Fisher rats were used in the experiments. Gastric ulcers were produced by injecting 50 microl of 20% acetic acid into subserosa of the border between the fundic and antral gland areas. The rats of the rebamipide group were fed a diet containing 60 mg kg(-1) day(-1) rebamipide and killed on days 10, 30, 60, 90, 120 and 150 after ulceration. Reverse transcription polymerase chain reaction of HGF, c-met, Cox-2 and EP2 gene and immunohistochemistry of proliferating cell nuclear antigen (PCNA) were performed.
In the rebamipide group, gastric ulcer index was significantly smaller than in the control group at each time-point except at 10 days (P < 0.05, each); up-regulation of HGF, c-met, Cox-2 and EP2 mRNA was also observed. The mRNA level of HGF was significantly correlated with that of Cox-2 and EP2 (P < 0.05, each). The PCNA-labelled epithelial cells in the rebamipide group were also greater than in the control group on days 10, 30, 90 and 120 (P < 0.05, each).
The study suggests that rebamipide has anti-ulcerative effects on gastric mucosal cells via up-regulation of HGF, c-met, Cox-2 and EP2.
瑞巴派特在临床上用作抗溃疡药物，在日本尤其如此。瑞巴派特的主要作用机制包括诱导前列腺素和清除自由基。由于前列腺素是肝细胞生长因子（HGF）的诱导剂，我们研究了瑞巴派特对乙酸诱导的胃溃疡（一种人类溃疡模型）中HGF、c-met、环氧合酶-2（Cox-2）和前列腺素E2受体（EP2）亚型表达的影响。
实验使用96只雄性Fisher大鼠。通过向胃底腺区和胃窦腺区交界处的浆膜下注射50微升20%的乙酸来制造胃溃疡。瑞巴派特组的大鼠喂食含60毫克/千克/天瑞巴派特的饲料，并在溃疡形成后的第10、30、60、90、120和150天处死。进行HGF、c-met、Cox-2和EP2基因的逆转录聚合酶链反应以及增殖细胞核抗原（PCNA）的免疫组织化学检测。
在瑞巴派特组中，除第10天外，各时间点的胃溃疡指数均显著低于对照组（各P<0.05）；还观察到HGF、c-met、Cox-2和EP2 mRNA的上调。HGF的mRNA水平与Cox-2和EP2的mRNA水平显著相关（各P<0.05）。在第10、30、90和120天，瑞巴派特组中PCNA标记的上皮细胞也多于对照组（各P<0.05）。
该研究表明，瑞巴派特通过上调HGF、c-met、Cox-2和EP2对胃黏膜细胞具有抗溃疡作用。
