阿魏酸对幽门螺杆菌致胃炎小鼠胃黏膜Wnt/β-catenin信号通路的影响

Effect of ferulic acid on Wnt/β-catenin signal pathway in mice with gastritis induced by Helicobacter pylori

目的 评估阿魏酸对幽门螺杆菌Helicobacter pylori致胃炎小鼠Wnt/β连环蛋白(β-catenin)信号转导通路的影响。方法 采用H. pylori和N-甲基-N’-硝基-N-亚硝基胍(MNNG)联合诱导法制备C57BL/6小鼠胃炎模型,分为模型组、铋剂四联(阳性药)和阿魏酸高、低剂量(100、50 mg·kg^(-1))组,另设对照组。ig给药4周后,通过尿素酶试验评价H. pylori的定植程度;通过ELISA试验检测肿瘤坏死因子α(TNF-α)、白细胞介素8(IL-8)的血清水平;通过免疫组化试验检测胃黏膜Wnt2、β-catenin的蛋白表达。结果 模型组H. pylori定植率100%,阿魏酸高、低剂量组H. pylori清除率显著增加为67%、64%(P<0.01);与模型组比较,阿魏酸高、低剂量可使胃炎动物血清TNF-α、IL-8水平显著降低(P<0.01),可明显下调胃黏膜中Wnt2、β-catenin的蛋白表达(P<0.01)。结论 阿魏酸具有减轻H. pylori定植程度、减轻胃黏膜炎症反应等作用,其作用机制与抑制Wnt/β-catenin信号通路的异常活化、下调炎症因子的高表达等有关。

Objective To evaluate the effect of ferulic acid(FA)on the Wnt/β-catenin signal pathway in mice with Helicobacter pylori-induced gastritis.Methods Gastritis model in C57BL/6 mice was prepared by a combination of H.pylori infection and MNNG inducement.Then mice with gastritis were divided at random into model group,FA high and low dose groups and positive group(bismuth potassium citrate+omeprazole+clarithromycin+amoxicillin).The normal group of mice was set up at the same time.After four weeks of oral administration of medicines,the H.pylori colonization in mice were evaluated by rapid urase test.The ELISA experiments were carried out to measure the TNF-αand IL-8 levels in sera of mice.The protein expression of Wnt2 andβ-catenin in gastric mucosa were determined by immunohistochemical test.Results The H.pylori colonization rate was 100%in the model group.Comparing with that of model group,H.pylori eradication rates in groups treated with high and low doses of FA were evidently increased to 67%and 64%,respectively(P<0.01).FA(100 and 50 mg·kg^(-1))evidently decreased the serum TNF-αand IL-8 contents of the gastritis animals,and the differences were statistically significant when compared with those of the model group(P<0.01).High and low doses of FA significantly reduced the protein expression of Wnt2 andβ-catenin in gastric mucosa of mice with gastritis comparing with those of model group(P<0.01).Conclusion FA could alleviate the degree of H.pylori colonization,relieve the inflammatory reaction and prevent the epithelial-mesenchymal transition,showing a protective effect on gastric mucosa in mice with H.pylori-induced gastritis.The prevention of abnormal activation of Wnt/β-catenin signal pathway and inhibition of inflammatory cytokines expression may explain the mechanisms of FA in treating gastritis.