过刊浏览

腺苷A2A受体在小鼠颅脑创伤与外周组织损伤模型中的作用差异

戴双双, 熊仁平, 杨楠, 李玮, 朱佩芳, 周元国

第三军医大学大坪医院野战外科研究所分子生物学中心,国家创伤、烧伤与复合伤重点实验室.重庆 400042

摘要

该文旨在探索腺苷A2A受体在颅脑创伤模型与外周创伤及放射损伤复合创伤中的作用差异。分别观察和检测野生型小鼠、A2A受体基因敲除小鼠以及给予A2A受体激动剂CGS21680治疗的小鼠在皮肤创伤、放射损伤复合创伤后的伤口愈合时间以及颅脑创伤后的神经功能缺损情况、伤侧皮层脑含水量、脑脊液中谷氨酸浓度。结果表明，CGS21680促进外周组织伤口的愈合，却加重颅脑创伤模型的神经功能损害，这与其促进谷氨酸释放有关。相反，A2A受体基因敲除显著延迟小鼠皮肤创伤、放射损伤复合创伤模型的伤口愈合，而在颅脑创伤模型中通过抑制谷氨酸的释放产生保护效应。该研究初步证实A2A受体激活促进谷氨酸大量释放可能是其在中枢损伤与外周损伤产生作用差异的机理之一，这为将来临床应用A2A受体激动剂减轻外周损伤，而用A2A受体拮抗剂减轻颅脑损伤提供了一定的实验依据。

关键词： A2A受体; 颅脑创伤; 创伤愈合; 放射损伤复合创伤

Different effects of adenosine A2A receptors in the models of traumatic brain injury and peripheral tissue injury

Dai Shuangshuang, Xiong Renping, Yang Nan, Li Wei, Zhu Peifang, Zhou Yuanguo

Molecular Biology Center, State Key Laboratory of Trauma, Burn and Combined Injury, Research Institute of Surgery and Daping Hospital, the Third Military Medical University.Chongqing 400042

Abstract

Recently, activation of the adenosine A2A receptors has been shown to exert protection against peripheral tissue injuries but aggravation in the central nervous system (CNS) injuries. To explore the different effects of adenosine A2A receptors and try to performsome new treatment strategies for peripheral tissue and CNS traumas, we constructed the mouse models of skin trauma, skin combined radiation-impaired wound and traumatic brain injury (TBI), respectively. Wild type mice and A2A receptor gene knockout mice were both used in the experiments. In skin trauma and combined radiation-impaired wound models, the time of wound healing was observed,while in TBI model, neurological deficit scores, water content in injured brain and glutamate concentration in cerebral spinal fluid (CSF)were detected at 24 h after TBI. The results showed that in skin trauma and combined radiation-impaired wound models, CGS21680(an agonist of the A2A receptors) promoted while A2A receptor gene knockout delayed the course of skin wound healing. On the contrary, in TBI model, A2A receptor gene knockout, not CGS21680, showed a protective role by inhibition of glutamate release.These data further indicate that promoting glutamate release may account for the different effects of A2A receptor activation in CNS injury and peripheral tissue injury models. These findings may provide some experimental evidence and a new strategy for clinical treatment of peripheral tissue damages by agonists of A2A receptors, while treatment of CNS injuries by antagonists of A2A receptors.

Key words: A2A receptor;traumatic brain injury;Wound healing;combined radiation-impaired wound

收稿日期：　　录用日期：

通讯作者：　　E-mail:

引用本文：

戴双双, 熊仁平, 杨楠, 李玮, 朱佩芳, 周元国. 腺苷A2A受体在小鼠颅脑创伤与外周组织损伤模型中的作用差异[J]. 生理学报 2008; 60 (2): 254-258.

Dai Shuangshuang, Xiong Renping, Yang Nan, Li Wei, Zhu Peifang, Zhou Yuanguo. Different effects of adenosine A2A receptors in the models of traumatic brain injury and peripheral tissue injury. Acta Physiol Sin 2008; 60 (2): 254-258 (in Chinese with English abstract).