[1]申倩伟,马迎春,李 倩,等.乙酰谷酰胺对创伤性颅脑损伤大鼠的作用及机制实验研究[J].陕西医学杂志,2025,54(2):187-191.[doi:DOI:10.3969/j.issn.1000-7377.2025.02.008]
　SHEN Qianwei,MA Yingchun,LI Qian,et al.Effect and mechanism of acetylglutamine on traumatic brain injury in rats[J].,2025,54(2):187-191.[doi:DOI:10.3969/j.issn.1000-7377.2025.02.008]
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乙酰谷酰胺对创伤性颅脑损伤大鼠的作用及机制实验研究
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《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
54
期数:
2025年2期
页码:
187-191
栏目:
基础研究
出版日期:
2025-02-05

文章信息/Info

Title:
Effect and mechanism of acetylglutamine on traumatic brain injury in rats
作者:
申倩伟1; 马迎春1; 李 倩1; 张文慧2
(1.邢台市中心医院,河北 邢台 054000; 2.保定第七医院,河北 保定 072150)
Author(s):
SHEN Qianwei1; MA Yingchun1; LI Qian1; ZHANG Wenhui2
(1.Xingtai Central Hospital,Xingtai 054000,China; 2.Baoding Seventh Hospital,Baoding 072150,China)
关键词:
创伤性脑损伤;  乙酰谷酰胺;  核因子e2相关因子2/血红素加氧酶-1通路;  认知障碍;  大鼠
Keywords:
Traumatic brain injury;  Acetylglutamine;  Nuclear factor erythroid 2-related factor 2/Heme oxygenase-1 pathway;  Cognitive impairment;  Rats
分类号:
R -33
DOI:
DOI:10.3969/j.issn.1000-7377.2025.02.008
文献标志码:
A
摘要:
目的:探讨乙酰谷酰胺对创伤性颅脑损伤(TBI)大鼠的作用及其可能的机制。方法:选取雄性SD大鼠54只,随机分为假手术组、模型组和乙酰谷酰胺组,每组各18只。建立大鼠TBI模型后,乙酰谷酰胺组大鼠腹腔注射乙酰谷酰胺20 mg/kg,假手术组和模型组注射1 ml 0.9%氯化钠溶液,连续干预7 d。于干预后7 d进行神经功能缺损量表(mNSS)评分。采用HE染色观察大鼠脑组织病理学改变。检测脑含水量及脑组织超氧化物歧化酶(SOD)和丙二醛(MDA)水平。采用TUNEL法检测大鼠海马CA1区神经细胞凋亡情况。采用Western blot检测脑组织中核因子e2相关因子2(Nrf2)/血红素加氧酶-1(HO-1)通路相关蛋白表达。干预后4周,各组大鼠进行Morris水迷宫实验和矿场实验检测认知功能。结果:模型组mNSS评分高于乙酰谷酰胺组(P<0.05)。HE染色结果显示,对照组脑组织细胞结构清晰完整,核仁清晰,分布均匀,细胞周围间隙无水肿。模型组大鼠脑组织神经细胞排列松散,细胞周围间隙水肿,部分细胞变性,细胞核空泡化。乙酰谷酰胺组脑组织水肿、细胞核空泡化程度减轻,细胞结构较清晰。假手术组、乙酰谷酰胺组、模型组脑含水量依次升高(均P<0.05)。与假手术组比较,乙酰谷酰胺组和模型组脑组织MDA水平依次升高,SOD水平依次下降(均P<0.05)。与假手术组比较,模型组和乙酰谷酰胺组大鼠海马CA1区神经细胞凋亡率上升,且乙酰谷酰胺组凋亡率较模型组降低(均P<0.05)。模型组脑组织Nrf2、HO-1蛋白表达水平低于假手术组(均P<0.05)。乙酰谷酰胺组脑组织Nrf2、HO-1蛋白表达水平高于模型组(均P<0.05)。与假手术组比较,模型组和乙酰谷酰胺组逃避潜伏期延长,站立次数、穿越平台次数和运动路程减少,且乙酰谷酰胺组逃避潜伏期短于模型组,站立次数、穿越平台次数和运动路程多于模型组(均P<0.05)。结论:乙酰谷酰胺能够减轻TBI大鼠脑水肿程度,抑制氧化应激反应,降低神经细胞凋亡,改善脑组织损伤及认知障碍,其作用机制可能与激活Nrf2/HO-1通路有关。
Abstract:
Objective:To investigate the effects of acetylglutamine on traumatic brain injury(TBI)in rats and explore its potential mechanisms.Methods:A total of 54 male SD rats were randomly divided into sham surgery group,model group and acetylglutamine group,with 18 rats in each group.A rat TBI model was established,and the acetylglutamine group was intraperitoneally injected with acetylglutamine at a dose of 20 mg/kg,while the sham surgery group and the model group were injected with 1 ml of 0.9% sodium chloride solution,with continuous intervention for 7 days.Neurological Deficit Scores(mNSS)were assessed after 7 days of intervention.HE staining was used to observe pathological changes in rat brain tissue.Brain water content and levels of superoxide dismutase(SOD)and malondialdehyde(MDA)in brain tissue were measured.TUNEL assay was used to detect apoptosis of neurons in the hippocampal CA1 region.Western blot was employed to detect the expression of proteins in the nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)pathway in brain tissue.Four weeks after intervention,Morris water maze test and mine field test were performed to detect cognitive function of rats in each group.Results:The mNSS score of the model group was higher than that of the acetylglutamine group(P<0.05).HE staining showed that the brain tissue cells in the control group were clearly and completely structured,with clear nucleoli,uniform distribution,and no edema in the intercellular spaces.In the model group,rat brain tissue showed loosely arranged neurons,edema in the intercellular spaces,some cell degeneration,and vacuolation of the cell nuclei.The acetylglutamine group showed reduced brain tissue edema and vacuolation,with clearer cell structures.Brain water content increased in the order of sham surgery group,acetylglutamine group and model group(all P<0.05).Compared with the sham operation group, the MDA levels increased and the SOD levels decreased sequentially in brain tissue in the acetylglutamine group and the model group(all P<0.05).Compared with the sham surgery group,the apoptosis rate of hippocampal CA1 neurons in the model group and the acetylglutamine group increased,and the apoptosis rate in the aceglutamide group was lower than that in the model group(all P<0.05).The expression levels of Nrf2 and HO-1 proteins in the brain tissue of the model group were lower than those in the sham surgery group(all P<0.05).The expression levels of Nrf2 and HO-1 proteins in the acetylglutamine group were higher than those in the model group(all P<0.05).Compared with the sham surgery group,both the model group and the acetylglutamine group had prolonged escape latency,reduced standing times,platform crossings and movement distance,with the acetylglutamine group having shorter escape latency and more standing times,platform crossings and movement distance than the model group(all P<0.05).Conclusion:Acetylglutamine can reduce brain edema in TBI rats,inhibit oxidative stress responses,decrease neuronal apoptosis,improve brain tissue damage and ameliorate cognitive impairments.Its mechanism of action may be related to the activation of the Nrf2/HO-1 pathway.

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备注/Memo

备注/Memo:
[基金项目]河北省卫生健康委员会医学科学研究计划项目(2023GH-1062); 河北省保定市科技计划项目(18ZF202)
更新日期/Last Update: 2025-02-04