小檗碱对大鼠急性脑梗死的治疗作用及其机制  

Therapeutic effect and mechanism of berberine on acute cerebral infarction in rats

作　　者：姚彦 谷聚贤[1] 赵丽[1] 李猛[1] 艾静怡 刘超[2] YAO Yan;GU Juxian;ZHAO Li;LI Meng;AI Jingyi;LIU Chao(Department 5 of Neurology,Cangzhou Central Hospital,Cangzhou 061001,China;不详)

机构地区：[1]沧州市中心医院神经内五科,河北沧州061001 [2]沧州市中心医院CT诊断科

出　　处：《山东医药》2023年第12期48-52,共5页Shandong Medical Journal

基　　金：沧州市科技计划项目(204106131)。

摘　　要：目的观察小檗碱对大鼠急性脑梗死的治疗作用,并探讨其作用机制。方法采用改良线栓法进行急性脑梗死模型制备,将造模成功的48只大鼠随机分为低剂量小檗碱组、高剂量小檗碱组、小檗碱+Wnt/β-连环蛋白(β-catenin)信号通路抑制剂(DKK-1)组、模型组各12只;另取12只大鼠作为假手术组(实验过程中仅暴露动脉血管,不结扎)。低、高剂量小檗碱组分别灌胃给予100、200 mg/kg的小檗碱;小檗碱+DKK-1组灌胃给予200 mg/kg小檗碱,同时腹腔注射2 mg/kg的DKK-1;假手术组和模型组大鼠灌胃10 mL/kg的生理盐水;每天给药1次,连续给药14 d。Zea-Longa评分法测定大鼠神经功能评分,氯化三苯基四氮唑法检测大鼠脑梗死体积百分比,末端脱氧核苷酸转移酶介导的dUTP-生物素切口末端标记法检测大鼠脑组织神经元凋亡情况,酶联免疫吸附法检测大鼠脑组织肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6),蛋白印迹法检测大鼠脑组织Wnt-1、糖原合成酶激酶-3β(GSK-3β)、β-catenin蛋白。结果与假手术组比较,模型组大鼠Zea-Longa评分及脑组织脑梗死体积百分比、神经元凋亡指数、TNF-α、IL-6、GSK-3β蛋白表达升高(P均<0.05),脑组织Wnt-1、β-catenin蛋白表达降低(P均<0.05);与模型组比较,低、高剂量小檗碱组大鼠Zea-Longa评分及脑组织脑梗死体积百分比、神经元凋亡指数、TNF-α、IL-6、GSK-3β蛋白表达降低(P均<0.05),脑组织Wnt-1、β-catenin蛋白表达升高(P均<0.05);与高剂量小檗碱组比较,小檗碱+DKK-1组大鼠Zea-Longa评分及脑组织脑梗死体积百分比、神经元凋亡指数、TNF-α、IL-6、GSK-3β蛋白表达升高(P均<0.05),脑组织Wnt-1、β-catenin蛋白表达降低(P均<0.05)。结论小檗碱可减轻急性脑梗死大鼠炎症反应,抑制神经元凋亡,保护其神经功能,高剂量效果更佳,其作用机制可能与激活Wnt/β-catenin信号通路有关。Objective To observe the therapeutic effect of berberine on acute cerebral infarction in rats and to ex⁃plore its mechanism.Methods The acute cerebral infarction model was established by modified suture-occluded meth⁃od,48 rats successfully modeled were randomly divided into the low-dose berberine group,high-dose berberine group,berberine+Wnt/β-catenin signaling pathway inhibitor(DKK-1)group,and model group,with 12 rats in each.Another 12 rats were selected as sham operation group(only artery vessels were exposed during the experiment,no ligature was per⁃formed).Rats in the low-dose,high-dose berberine groups were given 100 and 200 mg/kg berberine by intragastric admin⁃istration,respectively;rats in the berberine+DKK-1 group were given 200 mg/kg berberine by intragastric administration and 2 mg/kg DKK-1 by intraperitoneal injection;rats in the sham operation group and model group were given 10 mL/kg normal saline intragastrically;the drug was given once a day,for 14 days.Zea-Longa score was used to determine the neu⁃rological function score of rats,triphenyltetrazole chloride was used to determine the percentage of cerebral infarction vol⁃ume,and dUTP-biotin incision end labeling mediated by terminal deoxynucleotide transferase was used to detect the apop⁃tosis of neurons in the rat brain tissues;tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)were detected by en⁃zyme-linked immunosorbent assay,and Wnt-1,glycogen synthetase kinase-3β(GSK-3β),andβ-catenin protein were de⁃tected by Western blotting.Results Compared with the sham operation group,the Zea-Longa score,percentage of cere⁃bral infarction volume,neuronal apoptosis index of brain tissues,TNF-α,IL-6,and GSK-3βprotein expression in the model group increased(all P<0.05),and the expression levels of Wnt-1 andβ-catenin protein in the brain tissues de⁃creased(all P<0.05).Compared with the model group,the Zea-Longa score,percentage of cerebral infarction volume,neuronal apoptosis index of brain tissues,TNF-α,IL-6,and GSK-3βpr

关 键 词：小檗碱 急性脑梗死 Wnt-1蛋白 糖原合成酶激酶-3Β Β-连环蛋白 

分 类 号：R285.5[医药卫生—中药学] R743.33[医药卫生—中医学]