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(S)-4C3HPG 对小鼠中度颅脑创伤后急性期伤情的影响及机制

杨楠, 戴双双, 宁亚蕾, 陈星云, 赵艳, 李平, 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； 基础 部生物化学与分子生物学教研室，重庆 400038

摘要

本文旨在探讨代谢型谷氨酸受体调节剂(S)-4C3HPG 在颅脑创伤急性期中的作用。将C57BL/6 小鼠分为治疗组和对 照组，分别复制颅脑创伤模型，治疗组在致伤前30 min 使用低、中、高3 种剂量(1、5、10 mg/kg)的(S)-4C3HPG 行腹 腔注射，对照组使用生理盐水。致伤24 h 后进行神经功能缺损评定，干湿重法测定伤侧皮层脑含水量，高效液相色谱测 定脑脊液中谷氨酸浓度，实时荧光定量PCR 法测定伤侧皮层炎症因子TNF- α 和IL-1β mRNA 的表达水平。结果显示注射 (S)-4C3HPG 可减轻神经功能缺损(P<0.05)和脑水肿(P<0.01)，同时降低脑脊液中谷氨酸含量(P<0.01)和伤侧皮层TNF- α (P< 0.05)、IL-1β(P<0.05)的mRNA 水平，并且此效应存在量效依赖关系。本研究初步证实(S)-4C3HPG 可通过抑制谷氨酸释 放及炎症介质产生，从而减轻颅脑创伤急性期的损伤。

关键词： 谷氨酸代谢型受体; 颅脑创伤; 炎症; 谷氨酸

分类号：R651.1+5

[Effect of (S)-4C3HPG on brain damage in the acute stage of moderate traumatic brain injury model of mice and underlying mechanism.] [Ariticle in Chinese]

Yang Nan, DAI Shuang-Shuang, NING Ya-Lei, CHEN Xing-Yun, ZHAO Yan, LI Ping, ZHOU Yuan-Guo

Molecular Biology Center, State Key Laboratory of Trauma, Burn and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing 400042, China； Department of Biochemistry and Molecular Biology, Third Military Medical University, Chongqing 400038, China

Abstract

The aim of this study is to investigate the effect of (S)-4-carboxy-3-hydroxy-phenylglycine [(S)-4C3HPG], a mixed group I glutamate metabotropic receptor antagonist and a group II agonist, on impairment in a cortical impact model of traumatic brain injury (TBI) in mice and to elucidate the possible mechanisms. Mice were injected (i.p.) with saline, 1 mg/kg (S)-4C3HPG, 5 mg/kg (S)- 4C3HPG and 10 mg/kg (S)-4C3HPG (n=10 per group), respectively, at 30 min before moderate TBI. Neurological deficit scores, water content in injured brain and glutamate concentration in cerebral spinal fluid (CSF) were detected at 24 h after TBI. The expressions of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) mRNA in injured cortex were also detected by real-time RT-PCR. The results showed that the neurological deficits and cerebral edema were significantly attenuated in mice pretreated with (S)-4C3HPG (5 and 10 mg/kg respectively) compared with those in mice pretreated with saline. Furthermore, (S)-4C3HPG treatment also decreased the glutamate concentration in CSF and the expressions of TNF-α and IL-1β mRNA remarkably in a dose-dependent manner. These results suggest that (S)-4C3HPG treatment attenuates cortical impact-induced brain injury possibly via suppression of glutamate release and inhibition of excessive inflammatory cytokine production. These findings highlight the potential benefit of glutamate metabotropic receptor ligand for preventing TBI.

Key words: metabotropic glutamate receptor; craniocerebral trauma; inflammation; glutamate

收稿日期：2010-08-17　　录用日期：2010-10-11

通讯作者：周元国　　E-mail: ygzhou@cta.cq.cn

引用本文：

杨楠, 戴双双, 宁亚蕾, 陈星云, 赵艳, 李平, 周元国. (S)-4C3HPG 对小鼠中度颅脑创伤后急性期伤情的影响及机制[J]. 生理学报 2010; 62 (6): 555-559.

Yang Nan, DAI Shuang-Shuang, NING Ya-Lei, CHEN Xing-Yun, ZHAO Yan, LI Ping, ZHOU Yuan-Guo. [Effect of (S)-4C3HPG on brain damage in the acute stage of moderate traumatic brain injury model of mice and underlying mechanism.] [Ariticle in Chinese] . Acta Physiol Sin 2010; 62 (6): 555-559 (in Chinese with English abstract).