重度颅脑创伤后应用(S)-4C3HPG减轻小鼠颅脑损伤的作用  

Effect of(S)-4C3HPG on alleviating brain injury in severe traumatic brain injury and the underlying mechanisms

作　　者：王昊[1] 戴双双[2] 杨楠 周元国 许民辉[1] 

机构地区：[1]第三军医大学大坪医院野战外科研究所神经外科,重庆400042 [2]第三军医大学基础医学部生物化学与分子生物学教研室,重庆400042 [3]第七研究室创伤、烧伤与复合伤国家重点实验室,重庆400042

出　　处：《第三军医大学学报》2012年第3期192-195,共4页Journal of Third Military Medical University

基　　金：国家自然科学基金(30900587);重庆市自然科学基金(CSTC2009BB5317);第三军医大学青年创新基金(0656)~~

摘　　要：目的探讨重度颅脑创伤(severe traumatic brain injury,sTBI)后不同时间点使用谷氨酸释放调节剂(S)-4C3HPG对颅脑创伤急性期伤情的影响,以明确调节谷氨酸释放获得有效脑保护作用的最佳时间点。方法以自由落体撞击方法制作重度小鼠颅脑损伤模型,分别在小鼠致伤后15 min、1、3、6 h 4个时间点腹腔注射(S)-4C3HPG 5 mg/kg,观察了其对颅脑创伤后24 h时神经功能缺损评分、脑含水量、脑脊液中谷氨酸浓度及炎症因子TNF-α、IL-1βmRNA表达的影响。结果致伤后24 h检测(S)-4C3HPG药物处理15 min组和1 h组神经功能缺损[分别为(1.70±0.48)、(1.90±0.56)]显著低于对照组[(2.80±0.42),P<0.01],脑含水量[分别为(80.14±0.28)%、(80.17±0.52)%]显著低于对照组[(82.55±0.34)%,P<0.01],脑脊液中谷氨酸浓度[分别为(4.24±0.28)、(6.12±0.23)μmol/L]显著低于对照组[(9.03±0.32)μmol/L,P<0.01],炎症因子TNF-αmRNA的表达[分别为(0.722±0.160)、(0.793±0.122)]显著低于对照组[(1.006±0.125),P<0.01],IL-1βmRNA的表达[分别为(0.594±0.128)、(0.651±0.111)]显著低于对照组[(1.012±0.088),P<0.01],证明于致伤后15 min和1 h给予(S)-4C3HPG能明显减轻重度颅脑损伤,而于致伤后3 h和6 h给予(S)-4C3HPG与对照组比较,神经功能缺损、脑含水量、脑脊液中谷氨酸浓度及炎症因子TNF-α、IL-1βmRNA的表达无统计学差异,说明神经功能保护作用不明显。结论重度颅脑创伤后,尽早使用(s)-4C3HPG控制谷氨酸释放将有效减轻急性期的脑损伤。Objective To investigate the effect of （S）-4C3HPG （S-4-carboxy-3-hydroxyphenylg- lycine） on acute brain injury at different time points after severe traumatic brain injury （sTBI） in mice, and to elucidate the possible mechanisms. Methods Mice model of sTBI was established by bumpiness of free falling body, and the model mice were injected with （S）-4C3HPG, 5 mg/kg （i. p. n = 10 per group）, at 15 min, 1 h, 3 h and 6 h after sTBI, respectively. Neurological deficit scores, water content in injured brain and glutamate concentration in cerebral spinal fluid （CSF） were measured, and mRNA expressions of tumor necrosis faetor-α （TNF-ot） and interleukin-1β （IL-1β） in injured cortex were detected by Real-time PCR at 24 h after TBI. Results Neurological deficits[ （1.70±0.48） and （1.90 ±0.56） ] , cerebral edema[ （80.14 ± 0. 28 ） % and （80.17 -＋ 0.52 ） % ] and glutamate concentration in CSF [ （4.24 ± O. 28 ） μmol/L and （6.12±0. 23） μmol/L] were significantly attenuated or decreased in mice treated with （S）-4C3HPG at 15 rain and 1 h post sTBI as compared with those in the control group[ （2.80±0.42）, （82.55 ±0.34）% and （9.03 ± 0. 32） txmol/L ; P 〈 0.01 1. mRNA expressions of TNF-α [ （0. 722 ± 0. 160 ） and （0. 793 ± 0. 122 ） ] and IL-1β[ （0. 594 4- 0. 128 ） and （ 0.651 ± 0. 111 ） ] significantly were decreased in mice treated with （ S ） - 4C3HPG at 15 min and 1 h post sTB] as compared with those in the control group [（ 1. 006 ± O. 125 ） and（1. 012 ＋0.088） ; P 〈0. 01 ]. However, these changes were not significant in the groups of mice treated with （S）4C3HPG at 3 h or 6 h post sTBI as compared with those of the control group. Gonclusion （S）- 4C3HPG treatment at early stage alleviates acute brain injury in sTBI, and its mechanism is possibly related to suppression of glutamate release.

关 键 词：重度颅脑创伤 (s)-4c3HPG 谷氨酸 炎症因子 

分 类 号：R332[医药卫生—人体生理学] R651[医药卫生—基础医学]