高压氧联合谷氨酰胺对创伤性颅脑损伤大鼠神经功能和神经细胞凋亡情况的影响
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摘要
目的:观察高压氧(HBO)联合谷氨酰胺(GLN)对创伤性颅脑损伤(TBI)大鼠神经功能和神经细胞凋亡情况的影响,分析HBO联合GLN治疗TBI的价值和可能机制.方法:将健康雄性SD大鼠(n=50)以Feeney自由落体法建立TBI模型,选取建模成功的大鼠(n=40)作为实验动物,根据干预方式分为4组,即TBI组(普通肠内营养干预,n=10)、TBI+HBO组(普通肠内营养+高压氧,n=10)、TBI+GLN组(谷氨酰胺肠内营养,n=10)、TBI+HBO+GLN组(谷氨酰胺肠内营养+高压氧,n=10).另选健康雄性SD鼠(n=10)作为健康组.干预后以平衡木实验对大鼠神经功能进行客观评价,用TUNEL法测定各组大鼠神经细胞的凋亡情况,分析组间神经功能和神经细胞凋亡水平的差异.结果:健康组大鼠神经功能评分(0.46±0.04分)、凋亡指数(0.37%±0.09%)显著低于其他各组;TBI+HBO+GLN组大鼠神经功能评分(1.24±0.17分)、凋亡指数(8.83%±0.96%)显著低于TBI组、TBI+GLN组、TBI+HBO组;TBI+HBO组大鼠神经功能评分(2.11±0.42分)、凋亡指数(13.71%±1.41%)显著低于TBI组、TBI+GLN组;TBI+GLN组大鼠神经功能评分(2.96±0.64分)、凋亡指数(18.39%±1.65%)显著低于TBI组,差异有统计学意义(P<0.01).结论:HBO联合GLN能够改善TBI大鼠的神经功能,协同产生脑神经保护作用,其作用机制可能与二者能协同抑制神经细胞凋亡有关.
AIM: To investigate the effect of hyperbaric oxygen( HBO) combined with glutamine( GLN) on neurological function and neuronal apoptosis in traumatic brain injury( TBI) in rats and analyze their value and potential mechanisms in the treatment of TBI. METHODS: Fifty healthy male adult SD rats were used to establish TBI model by the free-fall method and forty of them were selected into the experiment. Selected rats were randomly divided into 4 groups: the TBI group( n = 10),the TBI+HBO group( n =10),the TBI + GLN group( n = 10),and the TBI + HBO + GLN group( n = 10). In addition,10 healthy adult male SD rats were picked as healthy group. After intervention,the neurological function of the rats was evaluated by beam balance test,and the neuronal apoptosis of rats was evaluated by in situ end labeling( TUNEL).The difference on neurological function and neuronal apoptosis of different groups were compared and analyzed. RESULTS: The neurological function score( 0.46±0.04) and the neuronal apoptosis rate( 0. 37% ± 0. 09%) in healthy group were significantly lower than that of other groups( all P<0.01); The neurological function score( 1. 24 ± 0. 17) and the neuronal apoptosis rate( 8. 83% ±0.96%) in TBI + HBO + GLN group were significantly lower than that of TBI group,TBI+GLN group and TBI+HBO group( all P<0.01); The neurological function score( 2. 11 ± 0. 42) and the neuronal apoptosis rate( 13. 71% ± 1. 41%) in TBI + HBO group were significantly lower than that of TBI group and TBI + GLNgroup( all P < 0.01); The neurological function score( 2. 96 ±0.64) and the neuronal apoptosis rate( 18.39% ±1.65%) in TBI+GLN group were significantly lower than that of TBI group,with statistically significant differences( P < 0. 01). CONCLUSION:HBO combined with GLN could effectively improve neurological function and protect neurons in the treatment of TBI,which may be related to synergistic inhibition of neuronal apoptosis.
AIM: To investigate the effect of hyperbaric oxygen( HBO) combined with glutamine( GLN) on neurological function and neuronal apoptosis in traumatic brain injury( TBI) in rats and analyze their value and potential mechanisms in the treatment of TBI. METHODS: Fifty healthy male adult SD rats were used to establish TBI model by the free-fall method and forty of them were selected into the experiment. Selected rats were randomly divided into 4 groups: the TBI group( n = 10),the TBI+HBO group( n =10),the TBI + GLN group( n = 10),and the TBI + HBO + GLN group( n = 10). In addition,10 healthy adult male SD rats were picked as healthy group. After intervention,the neurological function of the rats was evaluated by beam balance test,and the neuronal apoptosis of rats was evaluated by in situ end labeling( TUNEL).The difference on neurological function and neuronal apoptosis of different groups were compared and analyzed. RESULTS: The neurological function score( 0.46±0.04) and the neuronal apoptosis rate( 0. 37% ± 0. 09%) in healthy group were significantly lower than that of other groups( all P<0.01); The neurological function score( 1. 24 ± 0. 17) and the neuronal apoptosis rate( 8. 83% ±0.96%) in TBI + HBO + GLN group were significantly lower than that of TBI group,TBI+GLN group and TBI+HBO group( all P<0.01); The neurological function score( 2. 11 ± 0. 42) and the neuronal apoptosis rate( 13. 71% ± 1. 41%) in TBI + HBO group were significantly lower than that of TBI group and TBI + GLNgroup( all P < 0.01); The neurological function score( 2. 96 ±0.64) and the neuronal apoptosis rate( 18.39% ±1.65%) in TBI+GLN group were significantly lower than that of TBI group,with statistically significant differences( P < 0. 01). CONCLUSION:HBO combined with GLN could effectively improve neurological function and protect neurons in the treatment of TBI,which may be related to synergistic inhibition of neuronal apoptosis.
引文
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[17]李亚松,陈祥荣,邬树凯,等.谷氨酰胺抑制内质网应激反应改善大鼠创伤性颅脑损伤后神经功能[J].中华临床营养杂志,2017,25(1):47-52.
[18]王瑾,陆新健,郑康,等.谷氨酰胺对脓毒症大鼠脑功能的保护作用[J].临床麻醉学杂志,2013,29(3):271-274.
[19]付宪华,方大钊,董楠,等.高压氧联合谷氨酰胺治疗大鼠创伤性颅脑损伤的研究[J].中华航海医学与高气压医学杂志,2013,20(4):228-231.
[20]周苏键,彭慧平.高压氧对脑损伤后神经功能恢复作用的研究进展[J].吉林医学,2015,36(4):742-744.
[2]包龙,徐峰,凌伟华,等.创伤性颅脑损伤患者:急性胃肠损伤与营养支持--基于欧洲危重病医学会关于急性胃肠损伤定义及处理指南的思考[J].中国急救医学,2013,33(9):793-796.
[3]Palzur E,Vlodavsky E,Mulla H,et al.Hyperbaric oxygen therapy for reduction of secondary brain damage in head injury:an animal model of brain contusion[J].J Neurotrauma,2004,21(1):41-48.
[4]Fu X,Zhu M,Sun X,et al.Hyperbaric oxygen treatment and enteral nutrition support with glutamine relieves traumatic brain injury in the rats[J].Int J Clin Exp Med,2014,7(12):5686-5690.
[5]李茂林,王祝峰,章薇,等.红景天苷对大鼠颅脑损伤的保护作用研究[J].中华神经外科疾病研究杂志,2016,15(2):128-131.
[6]Dail WG,Feeney DM,Murray HM,et al.Responses to cortical injury:II.Widespread depression of the activity of an enzyme in cortex remote from a focal injury[J].Brain Res,1981,211(1):79-89.
[7]尹延庆,方琦,廖壮槟,等.灯盏花素对创伤性脑损伤模型大鼠脑组织中蛋白激酶C-γ表达的影响[J].中国组织工程研究,2015,19(49):7926-7931.
[8]马青,李亚,唐民科.线叶金雀花对小鼠脑缺血再灌注损伤的保护作用[J].北京中医药大学学报,2017,40(3):193-199.
[9]朱岁军,刘晨,王俊,等.早期常压高氧治疗对大鼠颅脑损伤后线粒体功能及细胞凋亡的影响[J].中华危重症医学杂志:电子版,2015,8(1):17-23.
[10]徐燊,刘家传,王春琳,等.缺氧预处理对大鼠创伤性颅脑损伤后内质网应激的影响[J].中华神经医学杂志,2016,15(5):452-457.
[11]谭玲.高压氧对新生大鼠缺氧缺血性脑损伤神经细胞凋亡及NF-κB表达的影响[J].四川医学,2015,36(8):1099-1102.
[12]李明,殷玉华,江基尧.急性脑损伤后神经细胞凋亡机制的研究进展[J].实用临床医药杂志,2013,17(7):156-159.
[13]Chazalviel L,Haelewyn B,Degoulet M,et al.Hyperbaric oxygen increases tissue-plasminogen activator-induced thrombolysis in vitro,and reduces ischemic brain damage and edema in rats subjected to thromboembolic brain ischemia[J].Med Gas Res,2016,6(2):64-69.
[14]Lu Y,Kang J,Bai Y,et al.Hyperbaric oxygen enlarges the area of brain damage in MCAO rats by blocking autophagy via ERK1/2 activation[J].Eur J Pharmacol,2014,728:93-99.
[15]修光辉,李秀玲,朱义超,等.高压氧治疗对急性脑外伤大鼠神经行为学及CREB表达的影响[J].中国医学创新,2016,13(12):5-9.
[16]Ramadan S,Lin A,Stanwell P.Glutamate and glutamine:a review of in vivo MRS in the human brain[J].NMR Biomed,2013,26(12):1630-1646.
[17]李亚松,陈祥荣,邬树凯,等.谷氨酰胺抑制内质网应激反应改善大鼠创伤性颅脑损伤后神经功能[J].中华临床营养杂志,2017,25(1):47-52.
[18]王瑾,陆新健,郑康,等.谷氨酰胺对脓毒症大鼠脑功能的保护作用[J].临床麻醉学杂志,2013,29(3):271-274.
[19]付宪华,方大钊,董楠,等.高压氧联合谷氨酰胺治疗大鼠创伤性颅脑损伤的研究[J].中华航海医学与高气压医学杂志,2013,20(4):228-231.
[20]周苏键,彭慧平.高压氧对脑损伤后神经功能恢复作用的研究进展[J].吉林医学,2015,36(4):742-744.