腺苷A2A受体在小鼠碌沫脑创伤与外周组织损伤模型中的作用差异.pdfVIP

254 生理学报 Acta Physiologica Sinica, April 25, 2008, 60 (2): 254-258 研究论文 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：本文旨在探索腺苷A2A 受体在颅脑创伤、皮肤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 迟小鼠皮肤创伤及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释放产生保护效应。本研究初 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：A 2 A 受体；颅脑创伤；创伤愈合；放射损伤复合创伤 中图分类号：R 6 4 Different effects of adenosine A2A receptors in the models of traumatic brain injury and peripheral tissue injury DAI Shuang-Shuang, XIONG Ren-Ping, YANG Nan, LI Wei, ZHU Pei-Fang, ZHOU Yuan-Guo* 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, China 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 perform some 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 2