[1]李志营,许鑫格,孙林林,等.依达拉奉右莰醇对创伤性颅脑损伤大鼠学习记忆能力及海马区神经细胞凋亡的影响[J].新乡医学院学报,2023,40(3):213-218.[doi:10.7683/xxyxyxb.2023.03.003]
 LI Zhiying,XU Xinge,SUN Linlin,et al.Effect of edaravone dexborneol on learning and memory ability and neuronal apoptosis in hippocampus of rats with traumatic brain injury[J].Journal of Xinxiang Medical University,2023,40(3):213-218.[doi:10.7683/xxyxyxb.2023.03.003]
点击复制

依达拉奉右莰醇对创伤性颅脑损伤大鼠学习记忆能力及海马区神经细胞凋亡的影响
分享到:

《新乡医学院学报》[ISSN:1004-7239/CN:41-1186/R]

卷:
40卷
期数:
2023年3期
页码:
213-218
栏目:
基础研究
出版日期:
2023-03-05

文章信息/Info

Title:
Effect of edaravone dexborneol on learning and memory ability and neuronal apoptosis in hippocampus of rats with traumatic brain injury
文章编号:
20230303
作者:
李志营1许鑫格2孙林林3武百强4王甜甜5王艺博6
(1.郑州市第七人民医院医务科,河南 郑州 450016;2.新乡医学院研究生学院,河南 新乡 453003;3.郑州市第七人民医院神经外科,河南 郑州 450016;4.郑州市第七人民医院康复科,河南 郑州 450016;5.郑州市第七人民医院神经内科,河南 郑州 450016;6.郑州市第七人民医院急诊科,河南 郑州 450016)
Author(s):
LI Zhiying1XU Xinge2SUN Linlin3WU Baiqiang4WANG Tiantian5WANG Yibo6
(1.Medical Department,the 7th People′s Hospital of Zhengzhou;2.Graduate School,Xinxiang Medical University;3.Department of Neurosurgery,the 7th People′s Hospital of Zhengzhou;4.Department of Rehabilitation,the 7th People′s Hospital of Zhengzhou;5.Department of Neurology,the 7th People′s Hospital of Zhengzhou;6.Department of Emergency,the 7th People′s Hospital of Zhengzhou)
关键词:
颅脑损伤细胞凋亡依达拉奉右莰醇学习记忆能力
Keywords:
craniocerebral injurycell apoptosisedaravone dexborneollearning and memory ability
分类号:
R651.1
DOI:
10.7683/xxyxyxb.2023.03.003
文献标志码:
A
摘要:
目的探讨依达拉奉右莰醇对创伤性颅脑损伤大鼠的学习记忆能力及海马区神经细胞凋亡的影响。
方法将 24只健康成年雄性Sprague-Dawley大鼠随机分为假手术组、颅脑损伤组、药物组,每组8只。颅脑损伤组和药物组大鼠采用Fenny′s自由落体打击法制备颅脑损伤模型,假手术组大鼠不进行自由落体击伤脑部,其他操作同颅脑损伤组和药物组。造模成功后,药物组大鼠给予依达拉奉右莰醇 5 mL·kg-1 腹腔注射,假手术组和颅脑损伤组大鼠给予等体积的生理盐水腹腔注射,均每日1次。造模72 h后,采用穿梭箱试验检测各组大鼠学习记忆能力,分析大鼠的主动逃避反应率及逃避反应时间。采用苏木精-伊红染色法观察各组大鼠海马区神经细胞形态变化,并计数各组大鼠海马区正常及死亡神经细胞。采用原位末端转移酶标记染色法检测各组大鼠海马区神经细胞凋亡情况,计数各组大鼠海马区神经细胞的凋亡细胞及正常细胞。
结果与假手术组比较,颅脑损伤组和药物组大鼠主动逃避反应率降低(P<0.05),逃避反应时间增多(P<0.05);与颅脑损伤组比较,药物组大鼠主动逃避反应率增高(P<0.05),逃避反应时间减少(P<0.05)。光学显微镜下可见,假手术组大鼠海马区神经细胞的细胞质均一,排列整齐,细胞形态正常,细胞质淡染,细胞核圆形或椭圆形,核仁清晰,染色均匀;颅脑损伤组大鼠海马区神经细胞排列疏松紊乱,细胞质空泡,细胞核出现紫色深染,可见核碎裂,核仁不清,可见大量呈梭形固缩、碎裂溶解细胞,正常形态的神经细胞数量较少;药物组大鼠海马区神经细胞排列稍紊乱,多数神经细胞形态正常,少量神经细胞梭形固缩,少量神经细胞的细胞核深染。与假手术组比较,颅脑损伤组和药物组大鼠海马区正常神经细胞数量显著减少(P<0.05),死亡神经细胞数量显著增多(P<0.05);与颅脑损伤组比较,药物组大鼠海马区正常神经细胞数量显著增多(P<0.05),死亡神经细胞数量显著减少(P<0.05)。 假手术组大鼠海马区脑组织可见极少量凋亡神经细胞,为浅棕色或棕黄色深染细胞,细胞萎缩及固缩,空泡收缩,细胞结构发生破坏;颅脑损伤组和药物组大鼠海马区神经细胞凋亡细胞数显著多于假手术组(P<0.05),未凋亡细胞数显著少于假手术组(P<0.05);药物组大鼠海马区神经细胞凋亡细胞数显著少于颅脑损伤组(P<0.05),未凋亡细胞数显著多于颅脑损伤组(P<0.05)。
结论依达拉奉右莰醇可改善颅脑损伤大鼠学习记忆能力,其机制可能与抑制颅脑损伤大鼠海马区神经细胞凋亡有关。
Abstract:
ObjectiveTo explore the effect of edaravone dexborneol on learning and memory ability and neuronal apoptosis in hippocampus of rats with traumatic brain injury.MethodsTwenty-four healthy adult male Sprague-Dawley rats were randomly divided into sham operation group,craniocerebral injury group and drug group,with 8 rats in each group.The rats in the craniocerebral injury group and the drug group were performed with Fenny′s freefall method to prepare the craniocerebral injury model.The rats in the sham operation group were not subjected to free fall injury to the brain,and other operations were same as those in the craniocerebral injury group and the drug group.After successful modeling,the rats in the drug group were injected intraperitoneally with 5 mL· kg-1 of edaravone dexborneol,and the rats in the sham operation group and craniocerebralinjury group was injected intraperitoneally with the same volume of normal saline,once a day.After 72 hours of modeling,the learning and memory ability of rats in each group was tested by shuttle box test,and the active escape reaction rate and escape reaction time of rats were analyzed.The morphological change of neurons in the hippocampus of rats in each group was observed by hematoxylin-eosin staining,and the number of normal and dead neurons in the hippocampus of rats was counted.The apoptosis of neurons in the hippocampus of rats was detected by in situ terminal transferase staining,and the number of apoptotic cells and normal cells in the hippocampus of rats in each group were counted.ResultsCompared with the sham operation group,the active escape reaction rate of rats in the craniocerebral injury group and drug group was significantly decreased (P<0.05),and the escape reaction time was significantly increased (P<0.05);compared with the craniocerebral injury group,the active escape reaction rate of rats in the drug group was significantly increased (P<0.05),and the escape reaction time was significantly decreased (P<0.05).Under the light microscope,the cytoplasm of neurons in the hippocampus of rats in the sham operation group was uniform and orderly arranged,the morphology of neurons was normal,the cytoplasm was light stained,the nucleus was round or oval,the nucleolus was clear,and the staining was uniform;the neurons in the hippocampus of rats in the craniocerebral injury group were arranged loosely and disorderly,with vacuoles in the cytoplasm,purple deep staining in the nucleus,nuclear fragmentation,unclear nucleolus,a large number of spindle-shaped pyknosis,fragmentation and dissolution cells,and a small number of neurons in normal morphology;the arrangement of nerve cells in the hippocampus of rats in the drug group was slightly disordered,most of the nerve cells were normal in morphology,a small number of nerve cells were spindle-shaped pyknosis,and a small number of nerve cells had hyperchromatic nuclei.Compared with the sham operation group,the number of normal nerve cells in the hippocampus of rats in the craniocerebral injury group and drug group was significantly decreased (P<0.05),and the number of dead neurons was significantly increased (P<0.05);comparedwith the craniocerebral injury group,the number of normal nerve cells in the hippocampus of rats in the drug group was significantly increased (P<0.05),and the number of dead neurons was significantly decreased (P<0.05).In the sham operation group,a small number of apoptotic neurons in the hippocampus of rats were found,which were light brown or brownish yellow hyperchromaticcells,with cell atrophy and pyknosis,vacuole contraction,and cell structure destruction.The number of apoptotic neurons in the hippocampus of rats in the craniocerebral injury group and drug group was significantly more than that in the sham operation group,while the number of non-apoptotic cells was significantly less than that in the sham operation group (P<0.05);the number of apoptotic neurons in the hippocampus of rats in the drug group was significantly less than that in the craniocerebral group (P<0.05),while the number of non-apoptotic cells was significantly more than that in the craniocerebral group (P<0.05).ConclusionEdaravone dexborneol can improve the learning and memory ability of rats with brain injury,and its mechanism may be related to the inhibition of neuronal apoptosis in the hippocampus of rats with brain injury.

参考文献/References:

[1] CAPIZZI A,WOO J,VERDUZCO-GUTIERREZ M.Traumatic brain injury:an overview of epidemiology,pathophysiology,and medical management[J].Med Clin North Am,2020,104(2):213-238.
[2] DAS A S,VICENTY-PADILLA J C,CHUA M M J,et al.Cerebrovascular injuries in traumatic brain injury[J].Clin Neurol Neurosurg,2022,223:107479.
[3] KHATRI N,THAKUR M,PAREEK V,et al.Oxidative stress:major threat in traumatic brain injury[J].CNS Neurol Disord Drug Targets,2018,17(9):689-695.
[4] CASH A,THEUS M H.Mechanisms of blood-brain barrier dysfunction in traumatic brain injury[J].Int J Mol Sci,2020,21(9):3344.
[5] ZHANG W,HONG J,ZHANG H,et al.Astrocyte-derived exosomes protect hippocampal neurons after traumatic brain injury by suppressing mitochondrial oxidativestress and apoptosis[J].Aging (Albany NY),2021,13(17):21642-21658.
[6] XU J,WANG A,MENG X,et al.Edaravone dexborneol versus edaravone alone for the treatment of acute ischemic stroke:a phase iii,randomized,double-blind,comparative trial[J].Stroke,2021,52(3):772-780.
[7] CHEN Q,CAI Y,ZHU X,et al.Edaravone dexborneol treatment attenuates neuronal apoptosis and improves neurological function by suppressing 4-HNE-Associated oxidative stress after subarachnoid hemorrhage[J].Front Pharmacol,2022,13:848529.
[8] BODNAR C N,ROBERTS K N,HIGGINS E K,et al.A systematic review of closed head injury models of mild traumatic brain injury in mice and rats[J].J Neurotrauma,2019,36(11):1683-1706.
[9] WEI G,WANG J,WU Y,et al.Sirtuin 1 alleviates neuroinflammation-induced apoptosis after traumatic brain injury[J].J Cell Mol Med,2021,25(99):4478-4486.
[10] ZHANG X S,LU Y,LI W,et al.Astaxanthin ameliorates oxidative stress and neuronal apoptosis via SIRT1/NRF2/Prx2/ASK1/p38 after traumatic brain injury in mice[J].Br J Pharmacol,2021,178(5):1114-1132.
[11] 孙林林,张兴祥,李建民,等.法舒地尔对大鼠蛛网膜下腔出血早期脑损伤的行为能力及海马区神经细胞凋亡的影响[J].中国老年学杂志,2019,39(5):2481-2484.
SUN L L,ZHANG X X,LI J M,et al.Effect of fasudil on behavioral ability and hippocampalnerve cell apoptosis after early brain injury in rats with subarachnoid hemorrhage[J].Chin J Gerontol,2019,39(5):2481-2484.
[12] DENG C,YI R,FEI M,et al.Naringenin attenuates endoplasmic reticulum stress,reduces apoptosis,and improves functional recovery in experimentaltraumatic brain injury[J].Brain Res,2021,1769:147591.
[13] 汤军,夏涛.大骨瓣开颅手术联合依达拉奉治疗重度颅脑损伤临床效果及对患者生活质量的作用[J].山西医药杂志,2021,50(6):906-909.
TANG J,XIA T.Clinical effect of large bone flap craniotomy combined with edaravone in the treatment of severe head injury and its effect on the quality of life of patients[J].Shanxi Med J,2021,50(6):906-909.
[14] SHAKKOUR Z,HABASHY K J,BERRO M,et al.Drug repurposingin neurological disorders:implications for neurotherapy in traumatic brain injury[J].Neuroscientist,2021,27(6):620-649.
[15] 梁新,王亚丽.依达拉奉右莰醇神经保护作用机制及临床应用进展[J].陕西医学杂志,2022,51(2):249-252.
LIANG X,WANG Y L.Neuroprotective mechanism and clinical application progress of edaravone dexborneol[J].Shaanxi Med J,2022,51(2):249-252.
[16] LI K,ZHANG Q,LU X,et al.Effects of butylphthalide sodium chloride injection combined with edaravone dexborneol on neurological function and serum inflammatory factor levels in sufferers having acute ischemic stroke[J].J Healthc Eng,2022,2022:1509407.
[17] 赵瑞亭,邢国平,于海宁,等.依达拉奉右莰醇治疗血管性痴呆的实验研究[J].河北医药,2022,44(17):2626-2629.
ZHAO R T,XING G P,YU H N,et al.Experimental study of edaravone dexborneol in the treatment of vascular dementia[J].Hebei Med J,2022,44(17):2626-2629.
[18] XU L,GAO Y,HU M,et al.Edaravone dexborneol protects cerebral ischemia reperfusion injury through activating Nrf2/HO-1 signaling pathway in mice[J].Fundam Clin Pharmacol,2022,36(5):790-800.
[19] 张亚洁,王炎强,牟英峰,等.依达拉奉右莰醇对脑缺血再灌注大鼠焦虑抑郁样行为的影响及机制[J].中华行为医学与脑科学杂志,2022,31(1):17-24.
ZHANG Y J,WANG Y Q,MU Y F,et al.Effect of edaravone dexborneol on anxious-and depressive-like behaviors and its mechanism in rats with cerebral ischemia-reperfusion[J].Chin J Behav Med Brain Sci,2022,31(1):17-24.
[20] SCHUMM S N,GABRIELI D,MEANEY D F.Plasticity impairment exposes CA3 vulnerability in a hippocampal network model of mild traumatic brain injury[J].Hippocampus,2022,32(3):231-250.
[21] LENGEL D,ROMM Z L,BOSTWICK A,et al.Glucocorticoid receptor overexpression in the dorsal hippocampus attenuates spatial learning and synaptic plasticity deficits after pediatric traumatic brain injury[J].J Neurotrauma,2022,39(13/14):979-998.
[22] 徐伟,张山,唐会昌,等.依达拉奉右莰醇对大鼠液压冲击脑损伤模型的神经保护作用[J].山西医科大学学报,2022,53(9):1142-1149.
XU W,ZHANG S,TANG H C,et al.Neuroprotective effect of edaravone dexcamphenol against hydraulic shock brain injury in rats[J].Shanxi Med Univ,2022,53(9):1142-1149.
[23] ZHANG M,TENG C H,WU F F,et al.Edaravone attenuates traumatic brain injury through anti-inflammatory and anti-oxidative modulation[J].Exp Ther Med,2019,18(1):467-474.
[24] SHAKKOUR Z,ISSA H,ISMAIL H,et al.Drug repurposing:promises of edaravone target drug in traumatic brain injury[J].Curr Med Chem,2021,28(12):2369-2391.
[25] OBENG E.Apoptosis(programmed cell death) and its signals-A review[J].Braz J Biol,2021,81(4):1133-1143.

相似文献/References:

[1]刘晓帆,史新江,杜心顺,等.颅脑损伤后铁代谢的改变及其意义[J].新乡医学院学报,1995,12(03):244.
[2]杨万才,王立东,周琦,等.细胞凋亡与食管贲门癌组织病理学特性的关系[J].新乡医学院学报,1996,13(04):326.
[3]杨万才,李健.细胞凋亡与消化系统疾病[J].新乡医学院学报,1997,14(02):186.
[4]程报国.外伤性脑梗塞48例临床分析[J].新乡医学院学报,2001,18(05):364.
[5]谭 军,杨廷桐,范琦芳.鼠脑局部缺血再灌注的形态学与细胞凋亡的研究[J].新乡医学院学报,2002,19(04):260.
[6]姜玲君.颅脑损伤后失语患者语言训练疗效探讨[J].新乡医学院学报,2002,19(05):439.
[7]张艳芬,范雪晖.细胞内外Ca2+对细胞凋亡的影响[J].新乡医学院学报,2003,20(03):193.
[8]张艳芬,范雪晖.细胞内外ca2+对细胞凋亡的影响[J].新乡医学院学报,2003,20(03):193.
[9]王莉莉,郭伟.重度颅脑损伤患者气管切开术后呼吸道护理 [J].新乡医学院学报,2007,24(03):304.
[10]胡云香.重型颅脑损伤患者鼻饲饮食的临床护理[J].新乡医学院学报,2008,25(05):522.

更新日期/Last Update: 2023-04-11