瑞巴派特对提高胃溃疡愈合质量的实验研究

目的 比较瑞巴派特、奥美拉唑及两种药物联合应用干预大鼠胃溃疡愈合质量.方法 建立大鼠胃溃疡模型40只,均分为对照、瑞巴派特、奥美拉唑和瑞巴派特联合奥美拉唑组,7 d后观察大鼠胃溃疡大体形态,超声探察溃疡胃壁全层结构,局部组织学形态及检测黏膜白细胞介素(IL)-8,前列腺素(PG)E2和丙二醛(MDA)含量.结果 ①超声探查显示,对照组溃疡指数为(22.3±1.8)mm2,瑞巴派特组为(9.2±1.0)mm2,奥美拉唑组为(9.8±1.3)mm2,联合治疗组为(4.8±1.2)mm2.对照组均比用药组高(P值均＜0.05),瑞巴派特组和奥美拉唑组均比对照组降低(P值均＜0.05).②离体组织超声探查显示,对照组胃壁厚度明显增加、层次结构模糊消失,用药组胃壁厚度部分恢复正常、胃壁各层次结构部分重建.③组织学表现,用药组溃疡侵袭范围、炎性细胞浸润程度均明显轻于对照组,且周边黏膜再生程度明显优于对照组.④对照组胃黏膜IL-8为(1387.8±132.6)pg/ml,瑞巴派特组为(970.0±91.6)pg/ml,奥美拉唑组为(1102.2±76.9)pg/ml,联合治疗组为(934.4±110.2)pg/ml.对照组均比各用药组高(P值均＜0.05),瑞巴派特组与联合治疗组比奥美拉唑组明显降低(P值均＜0.05).⑤对照组胃黏膜MDA为(13.0±2.6)nmol/ml.瑞巴派特组为(8.5±4.8)nmol/ml,奥美拉唑组为(9.4±1.4)nmol/ml,联合治疗组为(4.6±1.4)nmol/ml.奥美拉唑组与瑞巴派特组均明显高于联合治疗组,且低于对照组(P值均＜0.05).⑥对照组胃黏膜PGE2为(55.0±22.5)pg/ml,瑞巴派特组为(103.5±12.5)pg/ml,奥美拉唑组为(96.9±7.0)pg/ml,联合治疗组为(235.5±26.0)pg/ml.奥美拉唑组与瑞巴派特组均明显高于对照组·且低于联合治疗组(P值均＜0.05).结论 与奥美拉唑相比,瑞巴派特同样能促进溃疡愈合进程,提高溃疡愈合质量;联合应用奥美拉唑,以不同机制同时作用于溃疡愈合过程,能更好地兼顾溃疡愈合的速度和质量.

Effect of Rebamipide on the quality of gastric ulcer healing in rats

Objective To evaluate the effects of Rebamipide,Omeprazol and their combination in treatment of gastric ulcer.Methods Forty gastric ulcer models were induced by acetic acid and randomly divided into 4 groups with 10 in each.The rats in control,Rebamipide,Omeprazol and combination groups were received saline (3 ml/d),Rebamipide (60 mg/kg),Omeprazol (10 mg/kg) as well as Rebamipide combined with Omeprazol for 7 days,respectively.After sacrifice,size of the ulcer and focal layer structures were measured in vitro by using miniature probe ultrasonography(MPS),mucosal sections were stained with H-E for histological examination,levels of interleukin-8/ prostaglandin E2 (PGE2) and methylenedioxyamphet amine (MDA) were evaluated by ELISA and TBA,respectively. Results ① Miniprobe ultrasonography revealed that comparing to control group(22.3 ± 1.8)mm2], the maximal length of ulcer in Rebamipide (9.2 ± 1.0) mm2 ],Omeprazol (9.8 ± 1.3) mm2] and combination (4.8 ± 1.2 )mm2 ] groups were significantly reduced ( P＜0.05 ).② In vitro,MPS examination revealed that layer echo structure of gastric wall was partially rebuilt in three medication groups,③ Histopathologically,comparing to control group,ulcer range and inflammatory infiltration in all medication groups were less important.④ The mucosal level of IL-8 in control group (1387.8 ± 132.6)pg/ml] was higher than that in Rebamipide group(970.0 ± 91.6) pg/ml],Omeprazol group (1102.2±76.9)pg/ml] and combination group(934.4 ± 110.2) pg/ml] (P＜0.05).⑤ The mucosal level of MDA was (9.4±1.4)nmol/ml and (8.5 ± 4.8)nmol/ml in Omeprazol and Rebamipide groups, respectively,which was higher than that in combination group(4.6±1.4)nmol/ml-] and lower than that in control group(13.0±2.6)nmol/ml].⑥ The PGE2 level was significantly increased in Omeprazol, Rebamipide and combination groups (96.9 ± 7.0) pg/ml,( 103.5 ± 12.5 ) pg/ml,and(235.5 ± 26.0) pg/ m,respeetively] compared to control group(55.0±22.5)pg/ml,P＜0.05)].Conclusions Rebamipide, Omeprazol and combination regimen may improve quality of ulcerative healing by increasing level of PGE2 and decreasing levels of IL-8 and MDA in gastric mucosa,and this will result in potentially reducing the rate of ulcer recurrence.Combination regimen shows more anti-ulcer effect comparing to monotherapy.