TLR4/NF-κB/COX-2致炎信号通路对幽门螺杆菌相关性慢性萎缩性胃炎发生、发展的影响及机制研究

Effect and mechanism of TLR4/NF-κB/COX-2 inflammatory signaling pathway on the development and pathogenesis of Helicobacter pylori-associated chronic atrophic gastritis

目的探究TLR4/NF-κB/COX-2致炎信号通路对幽门螺杆菌(H.pylori)相关性慢性萎缩性胃炎(chronic atrophic gastritis,CAG)发生、发展的影响及机制。方法选取2017年6月至2018年7月我院消化内科收治的经临床胃镜和组织病理学活检检查确诊为H.pylori相关性慢性胃炎患者79例为本次研究对象,依据是否发生胃萎缩分为萎缩性胃炎组(40例)和非萎缩性胃炎组(39例)。另选取我院同时期健康体检者39名作为正常组。观察三组受试对象的组织病理学变化与H.pylori感染情况。分别采用qRT-PCR法和Western blotting法检测三组受试对象胃黏膜组织中TLR4、NF-κB p65、COX-2 mRNA和蛋白表达。分析萎缩性胃炎组患者胃窦、胃体、全胃不同胃黏膜萎缩病变程度与H.pylori感染和TLR4、p-NF-κB p65及COX-2表达的相关性。结果三组受试对象的一般临床资料差异无统计学意义(P>0.05)。与正常组比较,萎缩性胃炎组和非萎缩性胃炎组患者的胃黏膜组织病理损伤显著且H.pylori感染加剧,且萎缩性胃炎组较非萎缩性胃炎组更明显,差异有统计学意义(P<0.05)。qRT-PCR法和Western blotting法检测结果显示,萎缩性胃炎组和非萎缩性胃炎组患者的胃黏膜组织中TLR4、NF-κB p65、p-NF-κB p65和COX-2表达较正常组均显著上调,且萎缩性胃炎组较非萎缩性胃炎组上调明显,差异有统计学意义(P<0.05)。Pearson相关性分析结果显示,萎缩性胃炎组患者胃窦、胃体、全胃不同胃黏膜萎缩病变程度与H.pylori感染和TLR4、p-NF-κB p65及COX-2的表达呈正相关(P<0.05)。结论 CAG患者胃黏膜组织中TLR4/NF-κB/COX-2致炎信号通路的异常活化与疾病发生、发展显著相关,可用于CGA患者早期筛查及胃黏膜萎缩病变程度的预测指标,对CAG的早期发现和防治具有重要临床意义和价值。

Objective To investigate the effect and mechanism of TLR4/NF-κB/COX-2 inflammatory signaling pathway on the development of Helicobacter pylori(H.pylori)-associated chronic atrophic gastritis(CAG). Methods A total of 79 patients with H.pylori-associated chronic gastritis admitted to the Department of Gastroenterology of our hospital from Jun.2017 to Jul. 2018 were selected as the subjects of this study. The above patients were divided into atrophic gastritis group(40 patients) and non-atrophic gastritis group(39 patients) based on whether gastric atrophy occurred. At the same time, 39 cases of healthy physical examination in our hospital were selected as normal group. The histopathological changes and H.pylori infection in three groups were observed. The expressions of TLR4, NF-κB p65 and COX-2 mRNAs and proteins in gastric mucosa tissues of the three groups were detected by qRT-PCR and Western blotting, respectively. The correlation of different degrees of gastric mucosa atrophy with H.pylori infection and expressions of TLR4, p-NF-κB p65 and COX-2 in gastric antrum, gastric body and whole stomach of patients with atrophic gastritis group were analyzed. Results There was no significant difference in the general clinical data among the three groups(P>0.05). Compared with the normal group, the gastric mucosal tissue lesions were significantly increased and the H.pylori infection was aggravated in the atrophic gastritis group and the non-atrophic gastritis group, and the atrophic gastritis group was more obvious than the non-atrophic gastritis group, and the difference was statistically significant(P<0.05). The results of qRT-PCR and Western blotting showed that the expressions of TLR4, NF-κB p65, p-NF-κB p65 and COX-2 in gastric mucosa of patients with atrophic gastritis and non-atrophic gastritis were significantly up-regulated compared with normal group, and those in the atrophic gastritis group were significantly higher than the non-atrophic gastritis group, and the difference was statistically significant(P<0.05). The results of Pearson correlation analysis showed that the degree of gastric mucosal atrophy in gastric antrum, gastric body, and whole stomach of patients with atrophic gastritis was positively correlated with H.pylori infection and expressions of TLR4, p-NF-κB p65 and COX-2(P<0.05).Conclusion The abnormal activation of TLR4/NF-κB/COX-2 inflammatory signaling pathway in gastric mucosa of patients with CAG is significantly associated with the development of disease, and can be used for early screening of CGA patients and predictors of gastric mucosal atrophy. It has important clinical significance and value for the early detection and prevention of CAG.