11-羰基-β-乙酰乳香酸抗氧化胃保护作用及机制研究

Antioxidant Mediated Preventative Effect of Acetyl-11-Keto-beta-Boswellic Acid on Gastric Injury in Rats

目的:研究11-羰基-β-乙酰乳香酸(AKBA)的抗氧化作用及胃保护效果。方法:30只SD大鼠随机分为5组:正常组(生理盐水5 mL/kg),模型组(吲哚美辛48 mg/kg),西咪替丁组(100 mg/kg),低剂量AKBA组(100 mg/kg),高剂量AKBA组(200mg/kg)。预给药1小时后,用吲哚美辛(48 mg/kg)灌胃造模,评价溃疡指数(UI)、胃内容物酸度(p H)、胃壁黏液量(GWM)、前列腺素E2(PGE-2)及一氧化氮(NO)的含量,并检测超氧化物歧化酶(SOD)、过氧化氢酶(CAT)的活性,丙二醛(MDA)含量及核转录相关因子2(Nrf2)和血红素加氧酶1(HO-1)的表达量。结果:(1)与造模组相比,AKBA高剂量组(P<0.05)与西咪替丁组(P<0.001)显著降低了吲哚美辛诱导的胃粘膜损伤,AKBA低剂量组的差异无统计学意义;(2)AKBA与西咪替丁均显著升高胃内容物p H(P<0.001)(AKBA低剂量组P<0.05),增加GWM含量(P<0.001);(3)与造模组相比,AKBA及西咪替丁组均显著增高PGE-2及NO含量(P<0.001);(4)与造模组相比,AKBA及西咪替丁组均显著增高SOD活性(P<0.001)(AKBA低剂量组P<0.05)及CAT活性(P<0.001)并降低了MDA含量(P<0.001);(5)与造模组相比,AKBA高剂量组及西咪替丁组促进Nrf2及HO-1表达明显增高(P<0.05)。结论:AKBA有较好的胃保护效果,同时可以通过升高GWM、降低胃内容物p H,升高NO含量,阻止PGE-2的降低,同时恢复SOD、CAT的活性,降低MDA含量,促进Nrf2及HO-1的表达发挥胃黏膜保护的作用。

Objective：To investigate the protective effect and antioxidant effect of Acetyl-11-Keto-beta-Boswellic Acid （AKBA） in gastric injury in rats.Methods：All the 30 rats were divided evenly and randomly into the following 5 groups：control group （5 mL/kg physiological saline）,model group （5 mL/kg physiological saline）,cimetidine group （100 mg/kg）,L-AKBA group （100 mg/kg） and H-AKBA group （200 mg/kg）.One hour before administration of indomethacin,the vehicle,cimetidine and AKBA were given to each experimental group through administration by gavage.The gastro-protection effect was assessed by measuring ulcer index （UI）,gastric juice acidity （pH）,gastric wall mucus （GWM）,prostaglandin E2 （PGE-2） and nitric oxide （NO）.The antioxidant effects were measured through the activity of superoxide dismutase （SOD）,catalase （CAT） and the level of MDA.Meanwhile,the expression of Erythroid-2-related factor 2 （Nrf2） and heme oxygenase-1 （HO-1） were assessed.Results：① Compared with model group,UI was decreased significantly in H-AKBA group （P＜0.05） and cimetidine group （P＜0.001）,while the difference between L-AKBA group and model group were not statistical significance;② Compared with model group,and the GWM were increased markedly in both AKBA groups and cimetidine group （P＜0.001）,and pH were increased in H-AKBA group,cimetidine group （P＜0.001） and L-AKBA group （P＜0.05）;③ Compared with control group,the level of PGE-2 and NO were significantly increased in both AKBA groups and cimetidine group （P ＜0.001）.④ Compared with model group,the activity of SOD and CAT were increased in H-AKBA group,cimetidine group （P＜0.001）,and in L-AKBA group （P＜0.05）.Besides,the level of MDA were decreased in both AKBA groups and cimetidine group （P＜0.001）.⑤ The expression of Nrf2 and HO-1 were increased in H-AKBA group,cimetidine group （P＜0.05）.Conclusions：The AKBA could protect gastric from injury through increasing GWM and gastric juice acidity and the level of PGE-2 and NO.Besides,AKBA could prevent gastric from oxidative stress through increase the activity of SOD and CAT,and decrease the level of MDA.Meanwhile,AKBA could promote the expression of Nrf2 and HO-1 to protect gastric from acute injury.