CagA和VacA抑制胃黏膜上皮细胞的自噬并促进胃癌前病变的恶化  

CagA and VacA inhibit gastric mucosal epithelial cell autophagy and promote the progression of gastric precancerous lesions

作　　者：张家祥 王文霸 闫曙光[1] 李京涛 魏海梁 赵唯含 ZHANG Jiaxiang;WANG Wenba;YAN Shuguang;LI Jingtao;WEI Hailiang;ZHAO Weihan(Basic Medical College,Shaanxi University of Traditional Chinese Medicine,Xianyang Shaanxi 712046;Department of Hepatology,Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine,Xianyang Shaanxi 712000;Department of Gastroenterology,Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine,Xianyang Shaanxi 712000,China)

机构地区：[1]陕西中医药大学基础医学院,陕西咸阳712046 [2]陕西中医药大学附属医院肝病科,陕西咸阳712000 [3]陕西中医药大学附属医院消化科,陕西咸阳712000

出　　处：《中南大学学报（医学版）》2022年第7期942-951,共10页Journal of Central South University ：Medical Science

基　　金：国家自然科学基金(81804082)。

摘　　要：细胞毒素相关基因A(cytotoxin-associated gene A,CagA)与细胞空泡毒素A(vacuolating cytotoxin A,VacA)是幽门螺杆菌发挥致病作用的关键,也是促进胃癌前病变进展的高危因素。细胞自噬能稳定细胞内环境,抵御幽门螺杆菌感染,防止损伤的DNA累积,并能抑制胃癌前病变异型细胞的增殖。CagA和VacA通过多种方式抑制自噬上游信号活化与自噬溶酶体成熟,使胃癌前病变胃黏膜细胞的自噬受到抑制。这一变化可导致幽门螺杆菌无法被自噬而被有效清除,CagA与VacA也因此持续存在,并促进胃黏膜组织细胞的炎症、氧化应激、凋亡和胃癌前病变异型细胞的糖酵解活性与增殖等一系列恶性生物学过程。特异性抑制CagA和VacA活性的药物研究已成为防治与幽门螺杆菌相关的严重胃部疾病的新方向,并且涌现出了多种可治疗胃癌前病变的药物或成分,这可为未来胃癌前病变的治疗打开新局面。Cytotoxin-associated gene A(CagA)and vacuolating cytotoxin A(VacA)are the keys to the pathogenic role of Helicobacter pylori and the high-risk factors for the progression of gastric precancerous lesions.Autophagy can stabilize the intracellular environment,resist Helicobacter pylori infection,prevent the accumulation of damaged DNA,and inhibit the proliferation of gastric precancerous variant cells.However,CagA and VacA can inhibit the activation of upstream signals of autophagy and the maturation of autophagy-lysosomes in various ways,thus inhibiting the autophagy of gastric mucosal cells in precancerous lesions of gastric cancer.This change can cause Helicobacter pylori to be unable to be effectively cleared by autophagy,so CagA and VacA can persist and promote the inflammation,oxidative stress,apoptosis of gastric mucosal tissue cells,and the glycolytic activity and proliferation of variant cells in gastric precancerous lesions and a series of malignant biological processes.In recent years,the research on drugs specifically inhibiting the activities of CagA and VacA has become a new direction for the prevention and treatment of Helicobacter pylori-related severe gastric diseases,and a variety of drugs or components that can precisely and effectively regulate the factors for the treatment of gastric precancerous lesions are emerged,which opens a new strategy for the treatment of gastric precancerous lesions in the future.

关 键 词：幽门螺杆菌 毒力因子 自噬 胃癌前病变 胃癌 

分 类 号：R735.2[医药卫生—肿瘤]