丁基苯酞对缺血性脑损伤模型大鼠血脑屏障的影响

摘要

目的 观察大鼠全脑缺血后血脑屏障的改变以及丁基苯酞的干预作用,探讨其对缺血性脑损伤的防护作用机制.方法 选择120只SD大鼠,随机分为假手术组24只、脑缺血组24只、丁基苯酞组72只.采用四血管结扎的全脑缺血模型,制模成功后丁基苯酞组大鼠按腹腔注射剂量又分为丁基苯酞0.3 mg/kg组24只、丁基苯酞1.0mg/kg组24只、丁基苯酞3.0mg/kg组24只；检测脑组织依文思蓝(EB)含量、免疫组织化学法检测脑组织血管内皮生长因子(VEGF)表达、心脏取血计数循环内皮细胞数.结果 与假手术组比较,脑缺血组大鼠脑组织EB含量、VEGF表达、循环内皮细胞数明显升高(P＜0.05,P＜0.01)；与脑缺血组比较,丁基苯酞各剂量组大鼠脑组织EB含量、VEGF表达、循环内皮细胞数明显降低,以丁基苯酞3.0 mg/kg组最明显(P＜0.05,P＜0.01).结论 丁基苯酞通过降低大鼠全脑缺血后脑组织VEGF表达、降低循环内皮细胞数,从而降低血脑屏障的通透性,对缺血性脑损伤有保护作用.%Objective To study the underlying mechanism of DL-3-n-butylphthalide in protectingrnbrain against ischemic injury by observing its intervention effect on blood-brain barrier in rats. Methods One hundred and twenty SD rats were randomly divided into sham operation group(n = 24) ,cerebral ischemia group(n = 24) and DL-3-n-butylphthalide group(n = 72). A global cerebral ischemia model was established by ligating the 4 blood vessels. Rats in DL-3-n-butylphthalide group were further divided into 0. 3 mg/kg DL-3-n-butylphthalide group, 1. 0 mg/kg DL-3-n-bu-tylphthalide group, and 3. 0 mg/kg DL-3-n-butylphthalide group. Evans blue concentration and VEGF expression level in brain tissue were measured by immunohistochemistry. Circulating endo-thelial cells (CEO in heart tissue samples were counted. Results The evans blue concentration, VEGF expression level and the number of CEC were significantly higher in cerebral ischemia group than in sham operation group and significantly lower in different DL-3-n-butylphthalide-dose groups, especiaaly in 3. 0 mg/kg DL-3-n-butylphthalide group than in cerebral ischemia group(P<;0. 05 ,P<0. 01). Conclusion DL-3-n-butylphthalide protects brain against ischemic injury by decreasing the VEGF expression,the number of CEC and the permeability of blood-brain barrier in rats following global cerebral ischemia.