基于NLRP3炎症小体活化导致GES-1细胞焦亡探讨消化性溃疡“毒热”病理演变机制  

Exploration of the Pathological Evolution Mechanism of“Toxic Heat”in Peptic Ulcer Based on NLRP3 Inflammatory Body Activation Leading to Scorch Death of GES-1 Cells

作　　者：段金江 周丽杰 王鑫宇 肖景东[2] DUAN Jinjiang;ZHOU Lijie;WANG Xinyu;XIAO Jingdong(Liaoning University of Traditional Chinese Medicine,Shenyang 110847,Liaoning,China;The Fourth Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110103,Liaoning,China)

机构地区：[1]辽宁中医药大学,辽宁沈阳110847 [2]辽宁中医药大学附属第四医院,辽宁沈阳110103

出　　处：《辽宁中医药大学学报》2024年第3期37-41,共5页Journal of Liaoning University of Traditional Chinese Medicine

基　　金：国家自然科学基金项目(82074296);辽宁省教育厅基金项目(L202063)。

摘　　要：消化性溃疡(peptic ulcer,PU)是在炎症反应不断地刺激下形成的消化系统疾病,其主要原因是攻击因素和保护因素之间的失衡,造成对黏膜的损害。在消化性溃疡活动期,黏膜表面分布黄白苔、充血水肿、渗出坏死、肉芽生成,同时伴有大量以中性粒细胞为主的炎症细胞浸润,“毒热”的病理机制与炎症密切相关。含NLR家族PYRIN域蛋白3(NLR family,pyrin domain containing protein,NLRP3)炎症小体是一种固有免疫细胞(包括巨噬细胞等)的多蛋白复合物,负责激活炎症反应,在PU的炎症发生过程中具有重要作用。其过程是各种病原微生物和机体内外的危险信号,被细胞膜的模式识别受体(pattern recognition receptors,PRRs)识别,激活核因子-kappa B(nuclear factor-kappa B,NF-κB),促进生成天冬氨酸特异性半胱氨酸蛋白酶-1前体(pro-Caspase-1),使NLRP3炎症小体活化,生成天冬氨酸特异性半胱氨酸蛋白酶-1(Caspase-1),诱导细胞焦亡,使得胞内炎症性物质——白介素-1β(IL-1β)、白介素-18(IL-18)、高迁移率族蛋白B1(HMGB1)等释放至胞外,自身免疫启动从而引发级联炎症反应。该研究以期为“毒热”理论提供病理基础,丰富其科学内涵,为后续研究做理论上的探讨,为防治PU提供更有效的方式。Peptic ulcer(PU)is a digestive disease formed when a person is stimulated by an ongoing inflammatory response.The main cause is an imbalance between attacking and protecting factors,which causes damage to the mucous membrane.In the active stage of PU,yellow and white fur,hyperemia and edema,necrotic exudation and granulation are distributed on the mucosal surface,accompanied by a large number of neutrophil-based inflammatory cell infiltration.The pathological mechanism of“toxic heat”is closely related to inflammation.The NLR family,pyrin domain containing protein(NLRP3)inflammasome is a multi-protein complex of innate immune cells(including macrophages,etc.),which is responsible for activating inflammatory response.It plays an important role in the inflammatory process of PU.The process is that various pathogenic microorganisms and danger signals inside and outside the body are recognized by the pattern recognition receptors(PRRs)of the cell membrane,and nuclear factor-kappa B(NF-κB)is activated,to promote the formation of aspart-specific cysteine proteinase-1 precursor(pro-Caspase-1),activate the NLRP3 inflammasome,generate aspart-specific cysteine proteinase-1(Caspase-1),and induce cell pyrodeath.The intracellular inflammatory substances interleukin-1β(IL-1β),interleukin-18(IL-18),and high mobility group protein B1(HMGB1)are released to the outside of the cell,and the autoimmunity is activated to trigger a cascade of inflammation.This study aims to provide a pathological basis for the theory of“toxic heat”,enrich its scientific connotation,make theoretical discussion for the follow-up research,and provide a more effective way for the prevention and treatment of PU.

关 键 词：消化性溃疡 毒热 NLRP3炎症小体 细胞焦亡 以痈论治 溃得康颗粒 

分 类 号：R256.3[医药卫生—中医内科学] R573.1[医药卫生—中医学]