吉林大学学报(医学版) ›› 2019, Vol. 45 ›› Issue (04): 843-848.doi: 10.13481/j.1671-587x.20190417

• 基础研究 • 上一篇    

丁苯酞对急性缺血性脑卒中大鼠的脑保护作用及其机制

张晓璇, 朱江, 李佳佳, 焦光美, 单海雷, 赵亮, 窦志杰   

  1. 承德医学院附属医院神经内科, 河北 承德 067000
  • 收稿日期:2018-10-19 发布日期:2019-08-02
  • 通讯作者: 张晓璇,副主任医师(Tel:0314-2279596,E-mail:mystylezhao@163.com) E-mail:mystylezhao@163.com
  • 作者简介:张晓璇(1979-),女,河北省承德市人,副主任医师,医学硕士,主要从事脑血管病临床方面的研究。
  • 基金资助:
    河北省卫计委医学科学项目资助课题(20181160)

Protective effect of butylphthalide on brain in rats with acute ischemic stroke and its mechanism

ZHANG Xiaoxuan, ZHU Jiang, LI Jiajia, JIAO Guangmei, SHAN Hailei, ZHAO Liang, DOU Zhijie   

  1. Department of Neurology, Affiliated Hospital, Chengde Medical College, Chengde 067000, China
  • Received:2018-10-19 Published:2019-08-02

摘要: 目的:探讨丁苯酞对急性缺血性脑卒中大鼠的脑保护作用,阐明其对急性缺血性脑卒中的治疗机制。方法:48只SD大鼠随机分为假手术组、模型组(局灶性脑缺血大鼠模型)和丁苯酞组(局灶性脑缺血大鼠模型+丁苯酞治疗),每组16只。对各组大鼠进行神经症状评分测定,对大鼠脑组织进行HE染色,采用氯化三苯基四氮唑(TTC)测定脑梗死面积百分率,采用Western blotting法和逆转录-聚合酶链反应(RT-PCR)测定大鼠脑组织中肝细胞生长因子(HGF)、血管内皮细胞生长因子(VEGF)、基质金属蛋白酶2(MMP-2)、基质金属蛋白酶9(MMP-9)、核转录因子κB抑制蛋白α(IκBα)和核转录因子κB(NF-κB)亚单位p65(NF-κB p65)蛋白及mRNA表达水平。结果:假手术组大鼠脑组织无梗死灶形成,无神经功能缺损症状;与模型组比较,丁苯酞组大鼠脑梗死面积百分率和神经功能评分明显降低(P<0.01)。假手术组大鼠脑组织细胞结构完整、分布均匀;模型组大鼠脑组织大部分细胞坏死,胞浆破裂,细胞核破裂、凝缩;丁苯酞组大鼠脑组织少量细胞肿胀和坏死。与假手术组比较,模型组大鼠脑组织中HGF、VEGF、MMP-2、MMP-9和NF-κB p65蛋白及mRNA表达水平均明显降低(P<0.01),IκBα蛋白及mRNA表达水平明显升高(P<0.01);与模型组比较,丁苯酞组大鼠脑组织中HGF、VEGF、MMP-2、MMP-9和NF-κB p65蛋白及mRNA表达水平均明显升高(P<0.01),IκBα蛋白和mRNA表达水平明显降低(P<0.01)。结论:丁苯酞可改善急性缺血性脑卒中大鼠的神经功能,减少脑梗死面积,其机制可能与丁苯酞升高脑组织HGF水平,并通过干扰NF-κB信号通路而促进脑血管形成有关。

关键词: 丁苯酞, 缺血性脑卒中, 肝细胞生长因子, 血管内皮细胞生长因子, 基质金属蛋白酶, 核转录因子κB

Abstract: Objective:To investigate the protective effect of butylphthalide on the brain of the rats with acute ischemic stroke, and to elucidate its mechanism in the treatment of acute ischemic stroke. Methods:Forty-eight rats were randomly divided into sham operation group, model group (focal cerebral ischemia rat model) and butylphthalide group (focal cerebral ischemia rat model + butylphthalide treatment), with 16 rats in each group.The nerve symptom scores of the rats in various groups were determined, and the brain tissue was stained by HE staining; triphenyl four azole nitrogen chloride (TTC) was used to detect the percentage of cerebral infarction area; Western blotting method and reverse transcription-polymerase chain reaction (RT-PCR) were used to detect the expression levels of hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2), matrix metalloproteinases-9 (MMP-9), and nuclear transcription factor inhibiting protein kappa B alpha(IκBα), nuclear transcription factor kappa B (NF-κB) p65(NF-κB p65) protein and mRNA in the brain tissue of the rats. Results:In sham operation group, there were no infarction and neurological defect in the brain tissue. Compared with model group, the percentage of cerebral infarction area and the neurological function score of the rats in butylphthalide group were significantly decreased(P<0.01). The structure and distribution of brain tissue cells of the rats in sham operation group were intact and uniform; most of the cells in model group were necrotic, cytoplasmic rupture, nucleus rupture and condensation; a small number of brain cells in butylphthalide group were swollen and necrotic. Compared with sham operation group, the expression levels of HGF, VEGF, MMP-2, MMP-9, and NF-κB p65 protein and mRNA in the brain tissue of the rats in model group were significantly decreased (P<0.01), and the expression levels of IκBα protein and mRNA were significantly increased (P<0.01). Compared with model group, the expression levels of HGF, VEGF, MMP-2, MMP-9, and NF-κB p65 protein and mRNA in the brain tissue of the rats in butylphthalide group were significantly increased (P<0.01),and the expression levels of IκBα protein and mRNA were significantly decreased (P<0.01). Conclusion:Butylphthalide can improve the nerve function of the rats with acute ischemic stroke and reduce the area of cerebral infarction;its mechanism may be related to increasing the HGF level in the brain tissue and promoting the cerebral angiogenesis.

Key words: butylphthalide, ischemic stroke, hepatocyte growth factor, vascular endothelial growth factor, matrix metalloproteinase-2, matrix metalloproteinase-9, nuclear transcriptron factor-kappaB

中图分类号: 

  • R743.3