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丁苯酞对脑梗死预后的作用及突触可塑性机制研究

N-butylphthalide improves cerebral infarction outcomes via synaptic plasticity mechanisms
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摘要 目的探讨丁苯酞(NBP)对缺血性脑卒中(IS)预后的作用及相关机制。方法选取2020年10月至2023年8月在河北省人民医院神经内科治疗的急性脑梗死患者80例,将患者随机分为NBP治疗组(n=40)和常规治疗组(n=40),比较两组90 d神经功能缺损评分差异。进行动物实验,将C57BL/6小鼠分为假手术(Sham)组、电凝法构造远端大脑中动脉闭塞(dMCAO)组、NBP组,应用改良神经功能缺损评分(mNSS)评分评估行为学,使用高尔基染色可视化神经元树突和树突棘并计算各组的树突棘密度,蛋白印迹技术检测脑组织中髓鞘碱性蛋白(MBP)、髓鞘少突胶质细胞糖蛋白(MOG)、蛋白脂质蛋白(PLP)的变化并使用PPI网络分析查看各蛋白之间的联系。结果NBP治疗组在治疗90 d后的美国国立卫生研究院卒中量表(NIHSS)评分、改良Rankin量表(mRS)评分与常规治疗组相比降幅更为显著(P<0.05);小鼠行为学评分发现NBP组小鼠的mNSS评分显著低于dMCAO组;高尔基染色发现Sham组树突棘密度明显高于dMCAO组和NBP组,NBP组树突棘密度显著高于dMCAO组;蛋白印迹实验结果表明,与dMCAO组相比,NBP组的MBP、MOG、PLP蛋白表达水平显著升高。结论NBP可能通过增加树突棘密度以及改善突触可塑性,改善IS患者长期存在的神经功能损伤和身体功能障碍状况。 Objective Therapeutic effects of n-butylphthalide(NBP)on ischemic stroke prognosis and underlying mechanisms.Methods The study involved 80 patients with acute cerebral infarction who were treated in the Department of Neurology at Hebei General Hospital from October 2020 to August 2023.These patients were randomly divided into two groups:an NBP treatment group(n=40)and a conventional treatment group(n=40).The study aimed to compare the differences in neurological deficit scores between the two groups 90 days after treatment.C57BL/6 mice were divided into three groups:a Sham group,a group subjected to distal middle cerebral artery occlusion(dMCAO)via electrocoagulation,and an NBP group.Behavioral assessments were performed using the modified Neurological Severity Score(mNSS).Neuronal dendrites and dendritic spines were visualized using Golgi staining,and dendritic spine density was calculated for each group.Changes in the levels of myelin-related proteins-myelin basic protein(MBP),myelin oligodendrocyte glycoprotein(MOG),and proteolipid protein(PLP)-in brain tissue were detected by Western blotting.Protein-protein interaction(PPI)network analysis was employed to examine the interconnections among these proteins.Results Compared to the conventional treatment group,the NBP treatment group showed a more significant reduction in the NIHSS score and mRS score 90 days after treatment(P<0.05);Behavioral assessment in mice revealed that the mNSS scores were significantly lower in the NBP group compared to the dMCAO group;Golgi staining demonstrated that dendritic spine density was significantly higher in the Sham group than in both the dMCAO and NBP groups,while it was significantly higher in the NBP group than in the dMCAO group;Western blot analysis indicated that the expression levels of MBP,MOG,and PLP proteins were significantly increased in the NBP group compared to the dMCAO group.Conclusion NBP may ameliorate persistent neural deficits and physical disabilities in patients with ischemic cerebral infarction by increasing dendritic spine density and improving synaptic plasticity.
作者 王薪尧 路帆 董立朋 任艳艳 薛雁飞 贾艳丽 赵景茹 Wang Xinyao;Lu Fan;Dong Lipeng;Ren Yanyan;Xue Yanfei;Jia Yanli;Zhao Jingru(Department of Neurology,Hebei General Hospital,Shijiazhuang O50051,China)
出处 《脑与神经疾病杂志》 2025年第12期727-733,共7页 Journal of Brain and Nervous Diseases
基金 河北省自然科学基金(H2024307003) 国家自然科学基金(82001229) 政府资助临床医学优秀人才培养项目(ZF2023187)。
关键词 缺血性脑卒中 丁苯酞 神经功能恢复 突触可塑性 Ischemic stroke N-butylphthalide Neurological recovery Synaptic plasticity
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