丁苯酞对血管性认知障碍大鼠炎症因子的影响及对认知障碍的改善作用  

Effects of butylphthalide on inflammatory factors and improvement of learning and memory in rats with vascular cognitive impairment

作　　者：欧春影[1] 李晓宾[1] 郭靖[1] 朱亮[1] 许可[1] 王梦 安晓雷[1] Ou Chunying;Li Xiaobin;Guo Jing;Zhu Liang;Xu Ke;Wang Meng;An Xiaolei(Department of Neurology,Xuzhou Central Hospital/the Xuzhou School of Clinical Medicine of Nanjing Medical University,Xuzhou 221000,China)

机构地区：[1]徐州市中心医院、南京医科大学徐州临床医学院神经内科,江苏徐州221000

出　　处：《中华脑血管病杂志（电子版）》2024年第5期483-487,共5页Chinese Journal of Cerebrovascular Diseases(Electronic Edition)

基　　金：江苏省科技局基金(BL2014028);江苏省卫生健康委科研课题(Ym2023012);徐州市科技项目(KC22175)。

摘　　要：目的探讨丁苯酞对血管性认知功能障碍(VCI)大鼠血清炎症因子的影响及对认知功能的改善作用,阐明丁苯酞治疗VCI的具体机制。方法选用雌雄各49只的无特定病原体级SD大鼠,体质量为(170±20)g,2个月龄,随机选取雌雄各40只用于制作VCI大鼠模型。VCI大鼠模型采用反复夹闭双侧颈总动脉结合降压改良的方法制作。将造模成功的54只大鼠随机分为模型组、阳性药物组及丁苯酞治疗组,每组18只。假手术组大鼠不反复夹闭双侧颈动脉,其他手术流程同模型组,假手术组给予生理盐水灌胃。造模成功后7 d,模型组给予生理盐水灌胃,阳性药物组给予盐酸多奈哌齐药液灌胃,丁苯酞治疗组给予丁苯酞药液灌胃。连续给药30 d后,检测大鼠血清炎症因子肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-6的含量,同时应用Morris水迷宫方法[包括定位巡航实验(连续测试5 d)、空间探索实验及可视平台实验]测试大鼠的认知功能。采用方差分析和非参数检验分析定位巡航实验测得的寻找平台的逃避潜伏期、空间探索实验测得的首次穿越平台所需的时间、可视平台实验测得的寻找平台的时间以及各组大鼠炎症因子的数据,采用LSD法进行组间两两差异比较。结果治疗后,阳性药物组[第1~5天:(70.23±25.20)s、(68.44±19.29)s、(42.92±22.30)s、(32.33±21.42)s、(26.68±22.40)s]、丁苯酞治疗组[第1~5天:(62.81±19.73)s、(52.02±15.51)s、(35.55±12.80)s、(26.25±7.52)s、(19.28±6.17)s]和模型组[第1~5天:(96.23±6.67)s、(87.35±27.57)s、(77.90±20.56)s、(54.27±19.11)s、(49.01±27.26)s]的逃避潜伏期均在减少,阳性药物组和丁苯酞治疗组相比模型组缩短更加明显(F=23.950,P<0.001)。空间探索实验中,与模型组大鼠首次穿越平台所需时间[(27.45±13.69)s]相比,阳性药物组[(16.54±5.64)s]和丁苯酞治疗组[(15.28±4.86)s]显著缩短(P均<0.001)。可视平台实验中,阳性药物组[(15.64Objective To investigate the effects of butylphthalide on serum inflammatory markers in a rat model of vascular cognitive impairment(VCI),and to clarify the specific mechanism of butylphthalide.Methods A total of 49 specific pathogen-free Sprague-Dawley rats,aged two months and weighing approximately(170±20)grams,were randomly assigned,with 40 males and 40 females used for VCI rat model creation.The VCI rat model was established by repeated bilateral carotid artery occlusion combined with modified hypotension.The successfully modeled rats were randomly divided into three groups:model,positive control,and butylphthalide treatment.Sham-operated rats in the sham group underwent the same surgical procedures as the model group but without carotid occlusion,receiving only normal saline via oral gavage.Seven days after successful modeling,the model group received intragastric administration of normal saline,the positive drug group received intragastric administration of nimodipine hydrochloride solution,and the butylphthalide treatment group received intragastric administration of butylphthalide solution.After 30 days of continuous administration,serum levels of tumor necrosis factor-alpha(TNF-α)and interleukin(IL)-6 were measured,and cognitive function was assessed using the Morris water maze method[including positioning cruise experiment(5 consecutive days of testing),spatial exploration experiment,and visible platform experiment].ANOVA and non-parametric test were used to analyze the escape latency of seeking the platform measured by the positioning cruise experiment,the time required to cross the platform for the first time measured by the space exploration experiment,the time to find the platform measured by the visual platform experiment,and the TNF-α and IL-6 data of the brain tissue of the rats in each group.LSD method was used to compare pairwise differences between groups.Results After treatment,the escape latency of the positive drug group[1-5 d:(70.23±25.20)s,(68.44±19.29)s,(42.92±22.30)s,(32.33±21.42

关 键 词：丁苯酞 炎症因子 血管性认知功能障碍 

分 类 号：R749.13[医药卫生—神经病学与精神病学]