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干扰素激活基因15作为一种急性和慢性神经损伤的通用标记

王仁刚, KAUL Marcus, 张东贤

Del E. Webb神经科学、衰老与干细胞研究中心；感染与免疫疾病中心, Sanford-Burnham医学研究所, La Jolla, CA 92037, 美国

摘要

在中枢神经系统中干扰素(interferon, IFN)信号系统的激活通常与炎症相关。但是，在肌萎缩性侧索硬化症(amyotrophic lateral sclerosis, ALS)动物模型SOD1(G93A)小鼠的脊髓中，症状前阶段I型IFN激活基因(IFN-stimulated genes, ISGs)的高度激活可在没有明显炎症的情况下发生。为了确定同样的信号系统是否在其它神经损伤中也有增强，我们检测了一种IFN激活基因ISG15在急性和慢性神经损伤的小鼠模型中的蛋白表达水平。我们观察到ISG15蛋白在经受全脑缺血或创伤性脑损伤的小鼠以及过度表达HIV gp120蛋白的转基因小鼠的大脑中显著增加。以上结果提示，ISGs的激活是神经损伤的一种普遍特性，并且ISG15可成为一种适用于检测中枢神经系统神经损伤的生物标志。

关键词： 干扰素激活基因15; 神经损伤; 生物标志

分类号：R741.04

Interferon-stimulated gene 15 as a general marker for acute and chronic neuronal injuries

WANG Ren-Gang, KAUL Marcus, ZHANG Dong-Xian

The Del E. Webb Neuroscience, Aging, and Stem Cell Research Center； Infectious and Inflammatory Disease Center, Sanford-Burnham Medical Research Institute, La Jolla, CA 92037, USA

Abstract

Activation of interferon (IFN) signaling in the central nervous system (CNS) is usually associated with inflammation. However, a robust activation of type I IFN-stimulated genes (ISGs) at pre-symptomatic stages occurs in the spinal cord of SOD1(G93A) mice, an amyotrophic lateral sclerosis (ALS) animal model, without obvious signs of inflammation. To determine if the same signaling pathway is elevated in other types of neuronal injuries, we examined the protein expression levels of an IFN-stimulated gene, ISG15, in mouse models of acute and chronic neuronal injuries. We found that ISG15 protein was dramatically increased in the brains of mice subjected to global ischemia and traumatic brain injury, and in transgenic mice overexpressing HIV gp120 protein. These results suggest that activation of ISGs is a shared feature of neuronal injuries and that ISG15 may be a suitable biomarker for detecting neuronal injuries in the CNS.

Key words: interferon-stimulated gene 15; neuronal injury; biomarker

收稿日期：2012-08-10　　录用日期：2012-09-11

通讯作者：张东贤　　E-mail: dzhang@sanfordburnham.org

引用本文：

王仁刚, KAUL Marcus, 张东贤. 干扰素激活基因15作为一种急性和慢性神经损伤的通用标记[J]. 生理学报 2012; 64 (5): 577-583.

WANG Ren-Gang, KAUL Marcus, ZHANG Dong-Xian. Interferon-stimulated gene 15 as a general marker for acute and chronic neuronal injuries. Acta Physiol Sin 2012; 64 (5): 577-583 (in Chinese with English abstract).