目的在急性胃溃疡大鼠模型上评价丙氨酰谷氨酰胺二肽预防给药对不同因素所致大鼠急性胃溃疡的作用,探讨其可能作用机制。方法建立水浸应激、无水乙醇和幽门结扎所致急性胃溃疡大鼠模型。每种胃溃疡模型均选用60只SD大鼠,随机分为模型组、西咪替丁(0.1g/kg)组、麦滋林-S(1.0g/kg)组以及丙氨酰谷氨酰胺二肽低(0.5g/kg)、中(1.0g/kg)及高(1.5g/kg)剂量组。实验前分别给予不同药物灌胃,每天1次,连续3d。以溃疡指数、胃液量、胃酸、游离酸、总酸及胃蛋白酶活性等为评价指标,观察不同剂量丙氨酰谷氨酰胺二肽灌胃给药对实验性胃溃疡的治疗效果。结果在所选剂量范围内,丙氨酰谷氨酰胺二肽均可显著降低大鼠的溃疡指数(P〈0.01);高、中剂量丙氨酰谷氨酰胺二肽对溃疡的抑制作用与麦滋林-S基本相当。丙氨酰谷氨酰胺二肽还可显著抑制幽门结扎型大鼠胃液游离酸分泌(P〈0.01),降低胃蛋白酶活性(P〈0.05)。结论丙氨酰谷氨酰胺二肽对不同因素所致急性胃溃疡均具明确治疗效果;其抗胃溃疡作用机制除已知黏膜保护作用外,还可能与其对胃酸及胃蛋白酶抑制作用有关。
Objective To evaluate the protective effect of alanyl-glutamine dipeptide (Ala-Gln) on different acute gastric ulcer models in rats and investigate its possible mechanisms. Methods The gastric ulcer in rats was induced by waterimmersion restraint stress,ethanol and pylorus ligation. On each gastric ulcer model,sixty SD rats were randomly divided into six groups including the gastric ulcer control group, cimetidine (0.1 g/kg) and marzulene-S (1.0 g/kg) treatment groups,as well as 0.5, 1.0 and 1.5 g/kg Ala-Gln treatment groups. Before the gastric ulcer,different doses of drugs were administered intragastrically,once a day for 3 days. Ulcer index, gastric acid, gastric juice value, gastric acid, free acid, total acid and pepsin activity were used to evaluate and compare the protective effect of Ala-Gln and other anti-ulcer drugs. Results Ala-Gln significantly reduced the gastric ulcer index in all giving dose (P0.01)and its protective effect increased significantly with the climbing dose. In all three gastric ulcer models,the anti-ulcer effects of 1.0 and 1.5 g/kg Ala-Gln treatment groups were equal to that of marzulene-S. In addition, Ala-Gln also markedly inhibited the secretion of free acid (P0.01)and decreased the activity of pepsin (P0.05) on pylorus ligation gastric ulcer rats. Conclusion Ala-Gln has obviously anti-ulcer effect on different experimental gastric ulcer models. Except for the known protective effect on gastric mucosa,its anti-ulcer mechanisms may be related to its inhibitory effect on gastric acid and pepsin.