陈晓殷 李文静 朱卓丽 李雄娟 黄焕森

摘要：萄糖调节蛋白78（GRP78）是首个被发现的内质网分子伴侣，同时被视为内质网应激反应的经典标志性蛋白分子，在细胞内发挥多重功能。目前已在肿瘤、大脑缺血再灌注损伤等病理组织器官中发现GRP78异常上调表达，GRP78作为肿瘤与脑血管缺血性疾病的治疗靶点的应用前景不可忽视。本文主要从GRP78的分子结构、正常生理功能、涉及的内质网应激反应相关机制、GRP78与肿瘤、缺血再灌注损伤的预后等方面进行综述，旨在揭示GRP78的功能作用，明确其在肿瘤、缺血再灌注损伤发生发展过程中的作用。

关键词：GRP78;内质网应激;肿瘤;缺血再灌注损伤

中图分类号：R34                                   文献标识码：A                                   DOI：10.3969/j.issn.1006-1959.2020.20.008

文章编号：1006-1959（2020）20-0026-04

Study on the Role of Glucose Regulatory Protein 78

CHEN Xiao-yin1，LI Wen-jing1，ZHU Zhuo-li2，LI Xiong-juan2，HUANG Huan-sen2

（1.Department of Anesthesiology，the Second Clinical College of Guangzhou Medical University，Guangzhou 511436，Guangdong，China;

2.Department of Anesthesiology，the Second Affiliated Hospital of Guangzhou Medical University，Guangzhou 510260，Guangdong，China）

Abstract：Glucose regulatory protein 78 （GRP78） is the first endoplasmic reticulum molecular chaperone to be discovered， and it is also regarded as a classic protein molecule of endoplasmic reticulum stress response， which performs multiple functions in cells. At present， abnormally up-regulated expression of GRP78 has been found in tumors， cerebral ischemia-reperfusion injury and other pathological tissues and organs. The application prospect of GRP78 as a therapeutic target for tumors and cerebral ischemic diseases cannot be ignored. This article mainly reviews the molecular structure of GRP78，the normal physiological functions， the related mechanisms of endoplasmic reticulum stress response， GRP78 and tumors， and the prognosis of ischemia-reperfusion injury are reviewed in order to reveal the functional role of GRP78 and clarify its occurrence in tumors and ischemia-reperfusion injury role in the development process.

Key words：GRP78;Endoplasmic reticulum stress;Tumor;Ischemia-reperfusion injury

葡萄糖调节蛋白78（glucose regulated protein 78，GRP78）是热休克蛋白70（heat shock protein 70，Hsp70）家族成员之一，也被称为免疫球蛋白重链结合蛋白（immunoglobulin heavy chain binding protein， Bip）。近期大量研究表明GRP78参与内质网应激、肿瘤、脑缺血再灌注损伤的调节。本文主要就GRP78的分子结构和生理功能及其在内质网应激、肿瘤生长和治疗、脑缺血再灌注损伤中的调节作用及机制的研究进行综述。

1 GRP78的分子结构和正常生理功能

GRP78主要定位于内质网上，是细胞内质网腔蛋白质合成质控的重要分子伴侣，参与各种细胞的生理过程。GRP78有三个结构域，包括C端多肽的结合部位（peptide-binding结构域）、C末端活性调节区域和N端结合ATP的结构域（ATPase功能域）。Peptide-binding结构域结合未折叠或错误折叠的蛋白多肽，在蛋白质二硫键异构酶作用下可促进蛋白质形成正確的二硫键，保持正确的天然构象。……