幽门螺杆菌感染中“cagA—ANGPTL4”轴介导胃粘膜损伤的作用机制研究

幽门螺杆菌(Hp)感染与慢性胃炎乃至胃癌的发生发展密切相关，其毒力蛋白cagA介导的胃黏膜病理性损伤在上述疾病进展中发挥了重要作用，但具体调控及效应机制有待阐明。我们前期发现，在Hp相关胃炎中cagA能诱导一种非经典黏膜损伤性分子——类血管生成素样蛋白4(ANGPTL4)的表达上调，且其表达水平与胃粘膜损伤程度呈正相关，据此我们推测“cagA—ANGPTL4”轴可能介导了Hp相关胃粘膜损伤的病理进程。因此，本项目拟以“cagA—ANGPTL4”轴为研究对象，利用临床标本、动物模型，通过细胞学、免疫学及分子生物学等技术：(1)明确“cagA—ANGPTL4”轴在Hp感染中介导胃黏膜损伤的临床意义；(2)阐明cagA诱导胃粘膜表达ANGPTL4的调控机制；(3)揭示ANGPTL4介导胃黏膜损伤的效应机制。相关研究成果将进一步阐明Hp感染致胃黏膜损伤的机制，为临床治疗提供新的策略方法。

Helicobacter pylori (Hp) infection is an important factor of chronic gastritis and gastric cancer. The pathological lesion of gastric mucosa mediated by its virulence molecule cagA is the basis for the progress of the above diseases. However, the underlying mechanism of this is unclear. Our previous study found that cagA could induce the expression of a non-classical mucosa lesion molecular angiopoietin-like protein (ANGPTL4) in Hp-associated gastritis, and the level of ANGPTL4 was positively correlated with the degree of gastric mucosal injury. It is suggested that this "cagA—ANGPTL4" axis may mediate Hp-associated gastric mucosal damage. Therefore, we aim at this pathway, and intend to investigate (1) the clinical significance of "cagA-ANGPTL4" axis in gastric mucosal injury mediated by Hp infection; (2) the regulatory mechanism of cagA induced expression of ANGPTL4 in gastric epithelium in Hp infection; (3) the mechanism of ANGPTL4-mediated gastric mucosa damage in Hp infection. This study may clarify the new mechanism of gastric mucosa damage caused by Hp infection and provide new strategies for clinical treatment.