山奈素对小鼠乙醇型胃溃疡的影响及其机制  

Effect of kaempferol on ethanol induced gastric ulcer in mice and its mechanism

作　　者：吕帅宜 林开文 邓雨婷 张婉君 张钰苹 林桃姑 屈慧娟 魏娜[1] LÜShuaiyi;LIN Kaiwen;DENG Yuting;ZHANG Wanjun;ZHANG Yuping;LIN Taogu;QU Huijuan;WEI Na(College of Pharmacy, Hainan Medical University, Haikou Hainan 571199, China)

机构地区：[1]海南医学院药学院,海南海口571199

出　　处：《江苏大学学报（医学版）》2021年第6期517-521,540,共6页Journal of Jiangsu University：Medicine Edition

基　　金：国家自然科学基金面上项目(81660649);国家大学生创新创业项目(201911810030);海南省教育厅教改课题(Hnjg2018-46)。

摘　　要：目的:探究山奈素对小鼠乙醇型胃溃疡的影响及其潜在机制。方法:将60只SPF级昆明小鼠随机均分为6组,每组10只,分别为正常对照组,模型组,阳性对照组,山奈素低、中、高剂量组。正常对照组和模型组给予0.5%羧甲基纤维素钠,其他4组分别给予雷尼替丁(100 mg/kg)、低剂量山奈素(31.7 mg/kg)、中剂量山奈素(63.4 mg/kg)、高剂量山奈素(126.8 mg/kg);所有小鼠灌胃容积均为20 mL/kg,连续给药7 d;然后用无水乙醇10 mL/kg灌胃建立急性胃溃疡模型;采用溃疡指数评估胃黏膜损伤情况,ELISA法检测血清中环氧合酶-2(cyclooxygenase-2,COX-2)、前列腺素E2(prostaglandin E2,PGE2)、TNF-α、IL-1β、IL-6、NO含量,免疫印迹法检测胃组织COX-2、诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)、NF-κB p65蛋白表达。结果:与正常对照组比较,模型组小鼠胃黏膜出现明显的血斑和上皮细胞脱落;与模型组相比,山奈素组可显著降低胃溃疡指数且高剂量组优于中、低剂量组(P均<0.05)。与正常对照组相比,模型组炎症介质COX-2、PGE2、TNF-α、IL-1β、IL-6、NO血清含量明显升高,胃组织COX-2、iNOS、NF-κB p65蛋白表达明显增加(P均<0.05);与模型组相比,山奈素组胃组织COX-2、iNOS、NF-κB p65蛋白表达及血清中炎症介质含量均明显降低(P<0.05或P<0.01)。结论:山奈素对乙醇型胃溃疡具有保护作用,可能通过抑制NF-κB/COX-2通路,减少下游炎症因子TNF-α、IL-6、IL-1β含量,降低iNOS活性,进而抑制NO产生。Objective:To explore the effect of kaempferol on ethanol-induced gastric ulcer in mice and its potential mechanism.Methods:Sixty SPF Kunming mice were randomly divided into 6 groups with 10 mice in each group:normal control group,model group,positive control group,kaempferol low,medium and high groups,respectively.Normal control group and model group were given 0.5%sodium carboxymethyl cellulose,and other groups were given ranitidine(100 mg/kg),kaempferol low-dose(31.7 mg/kg),kaempferol medium-dose(63.4 mg/kg)and kaempferol high-dose(126.8 mg/kg),respectively.The gavage volume of all mice was 20 mL/kg,and the mice were continuously given the drug for 7 days.Then the acute gastric ulcer model was established by gavage with 10 mL/kg anhydrous ethanol.The gastric mucosal injury was assessed by ulcer index.The contents of cyclooxygenase-2(COX-2),prostaglandin E2(PGE2),TNF-α,IL-1β,IL-6 and NO in serum were detected by ELISA and the expression of COX-2,inducible nitric oxide synthase(iNOS)and NF-κB p65 protein in gastric tissue were detected by Western blotting.Results:Compared with the normal control group,the gastric mucosa of mice in the model group showed obvious blood spots and epithelial cells shedding.Compared with model group,kaempferol significantly decreased gastric ulcer index(P<0.05).Compared with normal control group,the contents of inflammatory mediators COX-2,PGE2,TNF-α,IL-1β,IL-6 and NO in model group were significantly increased,and the protein expressions of COX-2,iNOS and NF-κB p65 were significantly increased(P<0.05).Compared with model group,the protein expressions of COX-2,iNOS and NF-κB p65 and the content of inflammatory mediators in serum in kaempferine group were significantly decreased(P<0.05 or P<0.01).Conclusion:Kaempferol exerts a protective effect on ethanol-induced gastric ulcer,which may be related to down-regulating the contents of downstream inflammatory mediators TNF-α,IL-6 and IL-1β,reducing the activity of iNOS and inhibiting the production of NO by inhibiting NF-κB/COX-2

关 键 词：山奈素 乙醇型胃溃疡 NF-κB/COX-2通路 炎症因子 胃保护 

分 类 号：R-332[医药卫生]