(S)-4C3HPG对小鼠中度颅脑创伤后急性期伤情的影响及机制  

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

作　　者：杨楠[1] 戴双双[2] 宁亚蕾[1] 陈星云[1] 赵艳[1] 李平[1] 周元国[1] 

机构地区：[1]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 [2]第三军医大学基础部生物化学与分子生物学教研室,重庆400038

出　　处：《生理学报》2010年第6期555-559,共5页Acta Physiologica Sinica

基　　金：supported by the National Natural Science Foundation of China(No.30900587);the Natural Science Foundation of Chongqing(No.2009BB5317);the Youth Innovative Foundation of Third Military Medical University,China(No.0656)

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30min使用低、中、高3种剂量(1、5、10mg/kg)的(S)-4C3HPG行腹腔注射,对照组使用生理盐水。致伤24h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-1βmRNA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。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-1α（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.

关 键 词：谷氨酸代谢型受体 颅脑创伤 炎症 谷氨酸 

分 类 号：R651.15[医药卫生—外科学]