曲克芦丁调控核因子κB信号通路抑制脑梗死模型大鼠脑损伤及神经元凋亡  

Troxerutin modulates nuclear factor-kappaB signaling pathway to inhibit brain injury and neuronal apoptosis in cerebral infarction rats

作　　者：刘哲哲 于梅青 王婷婷 张敏 李百艳 Liu Zhezhe;Yu Meiqing;Wang Tingting;Zhang Min;Li Baiyan(Department of Neurology,Hengshui People’s Hospital,Hengshui 253800,Hebei Province,China;Hebei Provincial Hospital of Traditional Chinese Medicine,Shijiazhuang 050000,Hebei Province,China)

机构地区：[1]衡水市人民医院神经内科,河北省衡水市253800 [2]河北省中医院,河北省石家庄市050000

出　　处：《中国组织工程研究》2025年第6期1137-1143,共7页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金资助项目(81473268),项目负责人:张敏;河北省医学科学研究基金项目(20200410),项目负责人:李百艳。

摘　　要：背景:目前已有研究发现曲克芦丁对脑部疾病有明显的改善作用,但是关于曲克芦丁对脑梗死治疗及神经元细胞影响的研究较少。目的:探究曲克芦丁调控核因子κB信号通路对脑梗死大鼠脑损伤及神经元凋亡的作用机制。方法:选取清洁级大鼠50只,将其随机分为健康组、模型组、曲克芦丁+核因子κB激动剂组、曲克芦丁组、核因子κB抑制剂组,后4组均采用动脉结扎法建立脑梗死大鼠模型。健康组及模型组采用等量生理盐水灌胃处理,曲克芦丁+核因子κB激动剂组采用72 mg/kg曲克芦丁灌胃+20 mg/kg RANK腹腔注射干预,曲克芦丁组采用72 mg/kg曲克芦丁灌胃处理,核因子κB抑制剂组采用120 mg/kg核因子κB抑制剂二硫代氨基甲酸吡咯烷进行腹腔注射,各组给药均1次/d,均连续干预30 d。药物干预完成后24 h,采用Zea-longa检测大鼠神经功能损伤,苏木精-伊红染色观察脑组织病理改变,TUNEL法检测神经元凋亡,采用免疫印迹法及PCR检测核因子κB p65、核因子κB p50蛋白及mRNA表达水平。结果与结论:①与健康组比较,模型组大鼠神经功能评分、神经元凋亡率、核因子κB p65、核因子κB p50 mRNA及蛋白表达水平升高(P<0.05);②与模型组比较,曲克芦丁+核因子κB激动剂组神经功能评分、神经元凋亡率、核因子κB p65、核因子κB p50 mRNA及蛋白表达水平降低(P<0.05);③与曲克芦丁+核因子κB激动剂组比较,曲克芦丁组、核因子κB抑制剂组神经功能评分、神经元凋亡率、核因子κB p65、核因子κB p50 mRNA及蛋白表达水平降低(P<0.05),且曲克芦丁组与核因子κB抑制剂组比较无差异(P>0.05);④模型组大鼠脑组织有大量神经元细胞胞质空泡化,明显水肿和坏死现象及大量炎性细胞浸润现象;曲克芦丁+核因子κB激动剂组脑组织肿胀减轻,网状结构和固缩细胞减少,仍伴有部分水肿;曲克芦丁组及核因子κB抑制剂组脑组织肿胀�BACKGROUND:Troxerutin has been found to have a significant ameliorative effect on brain disorders,but there are fewer studies on the effects of troxerutin on the treatment of cerebral infarction and on neuronal cells.OBJECTIVE:To investigate the mechanism by which troxerutin regulates nuclear factor-κB signaling pathway to reduce brain injury and neuronal apoptosis in cerebral infarction rats.METHODS:Fifty clean grade rats were randomized into healthy group,model group,and troxerutin+nuclear factor-κB agonist group,troxerutin group,and nuclear factor-κB inhibitor group.Except for the healthy group,all other groups were used to establish a rat model of cerebral infarction by arterial ligation.The healthy and model groups were treated once a day with an equal amount of physiological saline by gavage.The troxerutin+nuclear factor-κB agonist group was intervened with 72 mg/kg troxerutin by gavage+20 mg/kg RANK intraperitoneally.The troxerutin group was treated with 72 mg/kg troxerutin by gavage.The nuclear factorκB inhibitor group was intervened intraperitoneally with 120 mg/kg nuclear factorκB inhibitor pyrrolidine disulfiram.Administration in each group was given once a day for 30 continuous days.Zea-longa was used to detect neurological damage in rats,hematoxylin-eosin staining was used to observe pathological changes,TUNEL was used to detect neuronal apoptosis,and immunoblotting and PCR were used to detect the expression of nuclear factor-κB p65 and nuclear factor-κB p50 at protein and mRNA levels,respectively.RESULTS AND CONCLUSION:Compared with the healthy group,the neurological function score,neuronal apoptosis rate,nuclear factor-κB p65,nuclear factor-κB p50 mRNA and protein expression levels were elevated in the model group(P<0.05).Compared with the model group,the neurological function score,neuronal apoptosis rate,nuclear factor-κB p65 and nuclear factor-κB p50 mRNA and protein expression levels were decreased in the troxerutin+nuclear factor-κB agonist group(P<0.05).Compared with the troxerut

关 键 词：脑梗死 曲克芦丁 核因子Kappa B 神经元凋亡 脑损伤 

分 类 号：R452[医药卫生—治疗学] R365[医药卫生—临床医学] R743