基于KCNQ1-KCNE2在胃癌发生中的作用探讨胃癌“脾虚”现代医学基础  

To Discuss the Pathogenesis Markers of‘Spleen Deficiency'base on the Role of KCNQ1-KCNE2 in the Occurrence of Gastric Cancer

作　　者：黎家琪 邹玺[1,3] 刘沈林 LI Jiaqi;ZOU Xi;LIU Shenlin(Affiliated Hospital of Nanjing University of Chinese Medicine,Jiangsu Nanjing 210029,China;Nanjing University of Chinese Medicine,Jiangsu Nanjing 210023,China;Jiangsu Collaborative Innovation Center of TCM Cancer Prevention and Treatment,Jiangsu Nanjing 210023,China)

机构地区：[1]南京中医药大学附属医院,江苏省中医院,江苏南京210029 [2]南京中医药大学,江苏南京210023 [3]江苏省中医药防治肿瘤协同创新中心,江苏南京210023

出　　处：《中医药临床杂志》2024年第11期2043-2048,共6页Clinical Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金资助项目(81973782);国家中医药管理局全国名中医传承工作室建设项目(No.2018-119);江苏省中医院高峰学术人才项目(y2021rc19);江苏省卫健委项目(ZD2022070)。

摘　　要：近年来胃癌发病率逐渐呈年轻化,随着筛查手段的进步,胃癌早筛率也逐年提升。胃癌发生发展的机制复杂多样,最经典的认知是“正常胃黏膜—慢性浅表性胃炎—慢性萎缩性胃炎—肠上皮化生、异型增生—胃癌”演变模式,治疗时采用中医辨证论治与西医手术、放化疗、靶向免疫有机结合的方法能有效延长患者生存期、提高生活质量,故从中西医结合角度探讨胃癌发病的病机对临床治疗胃癌具有一定参考价值。目前部分学者把癌症看作通道病,认为离子通道功能或表达异常是癌症发病的相关机制。其中KCNQ1-KCNE2钾离子通道异聚体(KCNQ1:Potassium Voltage-Gated Channel Subfamily Q Member 1;KCNE2:Potassium Voltage-Gated Channel Subfamily E Regulatory Subunit 2)数量的低表达、缺乏一定程度上能促进胃癌的发生发展,其机制与KCNE2缺失导致KCNQ1在壁细胞上位置改变、钾离子流向发生改变,抑制胃酸生成导致功能性萎缩、KCNE2缺乏导致细胞周期蛋白D1(Cyclin D1)表达上调等过程有关,同经典演变模式相似。中医病因病机角度,胃癌的发生与发展总体不离“脾虚”,“脾虚”日久成积的致病病机、证候表现等与KCNQ1-KCNE2异聚体异常诱发胃癌的一系列表现类似,“脾虚”现代医学解析与胃酸分泌减少、CyclinD1、部分离子通道等相关,故该文采用取象比类方法,旨在以功能性萎缩、Cyclin D1为切入点从病因病机方面探讨KCNQ1-KCNE2异聚体在胃癌发生中的作用机制,以此为基础尝试探讨胃癌“脾虚”病机的现代医学标志物基础。In recent years,the incidence of gastric cancer has gradually become younger.With the advancement of screening methods,the early screening rate of gastric cancer has also increased year by year.The mechanism of gastric cancer occurrence and development is complex and diverse.The most classic cognition is the evolution model of“normal gastric mucosa-chronic superficial gastritis-chronic atrophic gastritis-intestinal metaplasia,dysplasia-gastric cancer”.The organic combination of traditional Chinese medicine syndrome differentiation and treatment with Western medicine surgery,radiotherapy and chemotherapy,and targeted immunotherapy can effectively prolong the patient's survival and improve the quality of life.Therefore,exploring the pathogenesis of gastric cancer from the perspective of integrated traditional Chinese and Western medicine has a certain reference value for the clinical treatment of gastric cancer.At present,some scholars regard cancer as a channel disease and believe that abnormal ion channel function or expression is a related mechanism of cancer pathogenesis.Among them,the low expression and deficiency of KCNQ1-KCNE2 potassium channel heteromers(KCNQ1:Potassium Voltage-Gated Channel Subfamily Q Member 1;KCNE2:Potassium Voltage-Gated Channel Subfamily E Regulatory Subunit 2)can promote the occurrence and development of gastric cancer to a certain extent.The mechanism is related to the fact that KCNE2 deficiency leads to changes in the position of KCNQ1 on parietal cells,changes in the direction of potassium ion flow,inhibition of gastric acid production leading to functional atrophy,and KCNE2 deficiency leads to upregulation of cyclin D1 expression,which is similar to the classic evolution pattern.From the perspective of TCM etiology and pathogenesis,the occurrence and development of gastric cancer are generally inseparable from“spleen deficiency”.The pathogenesis and symptom manifestations of“spleen deficiency”accumulated over time are similar to a series of manifestations of gastric ca

关 键 词：脾虚 胃癌 钾离子通道蛋白 KCNQ1 KCNE2 

分 类 号：R273[医药卫生—中西医结合]