【摘要】 目的研究替普瑞酮对类固醇激素所致胃黏膜损伤的保护作用及其机制。方法50只雄性SD大鼠随机分为空白组、实验对照组、低剂量替普瑞酮组、中剂量替普瑞酮组和高剂量替普瑞酮组,每组10只。采用泼尼松龙皮下注射制备大鼠胃黏膜损伤模型,低、中、高剂量组替普瑞酮的剂量分别为50、100、200mg/kg,给药7d,每天1次。观察胃黏膜的病理变化,计算溃疡指数、胃黏膜组织学损伤指数,放射免疫法检测血浆内皮素1和胃黏膜前列腺素E2(PGE2)水平,Griess法检测血清NO含量。结果类固醇激素能引起胃黏膜显著出血性损伤,实验对照组大鼠溃疡指数中位数为44.5,组织学损伤指数中位数为5.5,明显高于空白组(均为0,均P<0.01);实验组大鼠血浆内皮素1水平为399pg/ml±74pg/ml,高于空白组(279pg/ml±56pg/ml,P<0.01);血浆NO水平(27μmol/L±5μmol/L)低于空白组(36μmol/L±5μmol/L,P<0.01);胃黏膜PGE2水平(154pg/mg±83pg/mg)低于空白组(337pg/mg±112pg/mg,P<0.01)。低、中、高剂量替普瑞酮组的溃疡指数中位数分别为32.5,23.0,23.0,均明显低于实验组(均P<0.01);组织学损伤指数中位数分别为3.0,3.0,1.5,均明显低于实验组(均P<0.01),内皮素1水平分别为299pg/ml±99pg/ml,284pg/ml±85pg/ml,189pg/ml±32pg/ml,均明显低于实验对照组(P<0.05,P<0.01,P<0.01);NO水平分别为56μmol/L±16μmol/L,62μmol/L±12μmol/L,83μmol/L±9μmol/L,均明显高于实验对照组(均P<0.01),高剂量替普瑞酮组胃黏膜PGE2水平为241pg/mg±65pg/mg,明显高于实验组154pg/mg±83pg/mg(P<0.05)。溃疡指数、组织学损伤指数和内皮素1水平随替普瑞酮剂量的增大而降低,血清NO、胃黏膜PGE2水平随替普瑞酮剂量的增大而升高。结论替普瑞酮对类固醇致胃黏膜损伤具有一定的保护作用,其机制可能与降低内皮素1水平和增加NO和PGE2生成有关。更多还原

【Abstract】 Objective To estimate the effects of teprenone on protecting gastric mucosa against steroids-induced damage. Methods Fifty male Sprague-Dawley rats were randomly divided into 5 equal groups: normal control group, undergoing gastric infusion of normal saline for 7 days and fasting since the 4 th day for 4 days; model control group, undergoing gastric infusion of normal saline for 7 days and fasting and hypodermal injection of prednisolone 40 mg/kg since the 4 th day for 4 days; low dose teprenone group, undergoing gastric infusion of teprenone 50 mg/kg for 7 days and fasting and hypodermal injection of prednisolone 40 mg/kg since the 4 th day; middle dose teprenone group, undergoing gastric infusion of teprenone 50 mg/kg for 7 days and fasting and hypodermal injection of prednisolone 40 mg/kg since the 4 th day; and high dose teprenone group, undergoing gastric infusion of teprenone 200 mg/kg for 7 days and fasting and hypodermal injection of prednisolone 40 mg/kg since the 4th day. Samples of gastric mucosa were taken out 24 hours after the last drug administration to calculate the ulcer index and observe the histological changes. Blood samples were collected from the abdominal cardinal vein. The levels of plasma ET-1 and prostaglandin E2 were examined by radioimmunoassay. Serum level of nitric oxide (NO) was determined by Griess method. Results In the model control group, the ulcer index, grade of histological lesions and ET-1 level increased significantly compared with the normal control group (44.5 vs. 0,5.5 vs. 0, and 399 pg/ml±74 pg/ml vs. 279 pg/ml±56 pg/ml,all P<0.01), the PGE2 level decreased significantly.(154 pg/mg±83 pg/mg vs 337 pg/mg±112 pg/mg, P<0.01), and the NO level did not changed significantly. In the 3teprenone groups, the ulcer index decreased (32.5,23.0, and 23.0 vs. 44.5, all P<0.01), grade of histological lesions decreased (3.0,3.0,and 1.5 vs. 5.5, all P<0.01), ET-1 level decreased (299 pg/ml±99 pg/ml,284 pg/ml±85 pg/ml,and 189 pg/ml±32 pg/ml vs. 399 pg/ml±74pg/ml, P<0.05,P<0.01, and P<0.01), the No level increased (56 μmol/L±16 μmol/L,62 μmol/L±12 μmol/L,and 83 μmol/L±9 μmol/L vs. 27 μmol/L±5 μmol/L, all P<0.01), and the PGE2 level increased (190 pg/mg±58 pg/mg,196 pg/mg±35 pg/mg,241 pg/mg±65 pg/mg vs. 154 pg/mg±83 pg/mg, P>0.05,P>0.05,and P<0.05) compared with the model control group. Conclusion Teprenone is a beneficial cytoprotective agent of gastric mucosa. Pretreatment with teprenone has gastroprotective effect against steroids-induced mucosal damage to a certain extent with a mechanism related to ET-1, NO, and PGE2 concentrations in blood or gastric mucosa.更多还原