褪黑素对消炎痛所致胃溃疡小鼠的保护作用机制

Protective mechanism of melatonin on indomethacin-induced gastric ulcer in mice

目的探讨褪黑素对消炎痛所致胃溃疡小鼠的影响及其作用机制。方法将40只BALB/c小鼠随机均分为对照组、溃疡组、低剂量褪黑素(1 mg/kg)组和高剂量褪黑素(5 mg/kg)组。采用ELISA方法测定各组小鼠胃组织总抗氧化态(TAS)、总氧化态(TOS)及炎症细胞因子水平;采用HE染色对各组小鼠胃黏膜损伤进行组织病理学分析;采用免疫印迹方法检测各组小鼠胃组织核因子-κB(NF-κB)和Caspase-3表达水平。结果与对照组比较,溃疡组小鼠TAS、TOS、氧化应激指数及胃组织肿瘤坏死因子-α、白细胞介素(IL)-1β、IL-6、IL-10水平、NF-κB和Caspase-3蛋白表达水平升高(P<0.05)。与溃疡组比较,低剂量和高剂量褪黑素组小鼠上述指标均有改善,且高剂量褪黑素组尤为显著(P<0.05)。结论褪黑素对消炎痛诱导小鼠胃溃疡具有保护作用,可能与NF-κB调节炎症细胞因子和细胞凋亡有关。

Aim To evaluate the effect of melatonin on indomethacin-induced gastric ulcer in mice.Methods Forty BALB/c mice were randomly divided into control group,ulcer group,low-dose melatonin(1 mg/kg)group,and high-dose melatonin(5 mg/kg)group,with 10 mice in each group.Total antioxidant status(TAS),total oxidation status(TOS)and inflammatory cytokines in gastric tissue of mice in each group were determined by ELISA.HE staining was used to analyze the histopathological changes of gastric mucosa.Nuclear factor-kappa B(NF-κB)and Caspase-3 expression was detected by Western blotting.Results Compared with control group,the levels of TAS,TOS and OSI in ulcer group were increased(P<0.05).The levels of tumor necrosis factor-α(TNF-α),interleukin(IL)-1β,IL-6 and IL-10 were increased in gastric tissue of mice in ulcer group(P<0.05).The expression of NF-κB and Caspase-3 protein in gastric tissue of mice in ulcer group were increased(P<0.05).Compared with ulcer group,the above indexes of the low-dose and high-dose melatonin group were improved,and the indexes in high-dose melatonin group were particularly significant(P<0.05).Conclusion Melatonin has protective effect on indomethacin-induced gastric ulcer in mice,which may be related to NF-κB to regulate inflammatory cytokines and cell apoptosis.