TLR4/NF-κB通路在Hp诱导胃癌发生中的作用

The Role of TLR4/NF-кB Pathway in Hp Induced Gastric Cancer

目的观察Hp感染在慢性萎缩性胃炎(CAG)癌前病变发生发展中对TLR4/NF-KB通路的影响及其在慢性萎缩性胃炎癌前病变发生发展中的作用机制。方法60只Wistar大鼠随机分为正常组、模型组、Hp组,其中模型组、Hp组采用“MNNG+雷尼替丁+乙醇+饥饱失调”的综合方法复制Wistar大鼠CAG癌前病变模型,观察大鼠胃黏膜组织形态特征,并采用Western blot方法检测胃黏膜组织中TLR4、MyD88、细胞核因子kB(NF-кB)的表达水平,采用固相夹心法、酶联免疫吸附法检测白介素-8(IL-8)、肿瘤坏死因子-α(TNF-α)、干扰素-γ(IFN-γ)、白介素-1β(IL-1β)表达水平。结果较正常组的大致正常胃黏膜相比,Hp组的胃黏膜出现明显的肠上皮化生,模型组胃黏膜出现轻度萎缩伴肠上皮化生;模型组与Hp组IL-8、TNF-α、IFN-γ、IL-1β表达水平均明显高于正常组(P<0.01),且Hp组表达高于模型组(P<0.05)。结论Hp通过调节TLR4/NF-KB通路的表达水平促进胃黏膜的肠上皮化生及CAG的发展,进而可能促进胃癌的形成。

Objective To observe the effect and mechanism of Hp infection on TLR4/NF-кB pathway in precancerous lesion of chronic atrophic gastritis(CAG).Methods 60 Wistar rats were randomized into normal group,model group and HP group.The model group and HP group used the comprehensive method of“MNNG+ranitidine+ethanol+appetite maladjustment”to duplicate Wistar rat models of CAG precancerous lesion.We observed the morphologic characteristics of gastric mucosa in rats,and detected the expression of TLR4,MyD88,NF-кB in gastric mucosa by Western blot and the expression of IL-8,TNF-α,IFN-γand IL-1βby sandwich ELISA.Results Compared with the normal gastric mucosa in the normal group,the gastric mucosa of the Hp group showed obvious intestinal metaplasia,and the gastric mucosa of the model group showed mild atrophy with intestinal metaplasia.The expressions of IL-8,TNF-α,IFN-γ,IL-1βin the model group and Hp group were significantly higher than the normal group(P<0.01),and the expression in the Hp group was higher than the model group(P<0.05).Conclusion Hp can promote the development of intestinal metaplasia and CAG by regulating the expression of TLR4/NF-кB pathway,which may promote the formation of gastric cancer.