《生命科学》 2022, 34(4): 357-364

胞外组蛋白/循环组蛋白病理生理效应及相关机制

王丽君¹ , 余卫平^1,* , 程振兴^2,*

¹东南大学医学院病理生理学系，南京 210009 ²安徽医科大学第一附属医院消化内科，合肥 230022

摘　要：

组蛋白是染色质结构蛋白，也参与调节真核细胞基因表达。一旦发生大量细胞死亡，组蛋白会释放至细胞外成为胞外组蛋白或进入血液成为循环组蛋白，成为损伤相关分子模式(damage-associated molecular patterns, DAMPs)。胞外组蛋白/ 循环组蛋白结合并破坏细胞膜，激活细胞膜 Toll 样受体(Toll-like
receptors, TLRs) 如 TLR2、TLR4 和 TLR9，促进凝血酶或血小板活化，导致接触性细胞毒性、严重炎症反应和血栓形成，最终导致多器官损伤和功能障碍。该文主要综述近期报道的胞外组蛋白/ 循环组蛋白在各种疾病中的病理生理效应和机制以及作为治疗靶点的可能性。

通讯作者：余卫平 , Email:yuweiping@seu.edu.cn 程振兴 , Email:chengzhenxing407@163.com

Extracellular histone/circulating histone and its pathophysiological effects and mechanisms

WANG Li-Jun¹ , YU Wei-Ping^1,* , CHENG Zhen-Xing^2,*

¹Department of Pathophysiology, School of Medicine, Southeast University, Nanjing 210009, China ²Department of Gastroenterology, the First Affiliated Hospital of Anhui Medical University, Hefei 230032, China

Abstract:

Histones are structural proteins of chromatin and also involved in regulating gene expression in living eukaryotic cells. Once a large number of cell death occurs, histones are released outside the cells to become extracellular histones or into the blood to become circulating histones, which act as damage-associated molecular patterns (DAMPs). Extracellular histones/circulating histones bind and interrupt cell membrane, activate membrane Toll-like receptors (TLRs) such as TLR2, TLR4 and TLR9, and enhance thrombin or platelet activation, which cause cytotoxicity of the cells contacted, severe inflammatory reaction, and thrombosis, and eventually lead to injury and dysfunction of multiple organs. This paper mainly reviews the recently reported pathophysiological roles and mechanisms of extracellular histones/circulating histones in various diseases, as well as the possibility of being used as a therapeutic target.

Communication Author：YU Wei-Ping , Email:yuweiping@seu.edu.cn CHENG Zhen-Xing , Email:chengzhenxing407@163.com