原花青素对脑缺血再灌注小鼠脑组织细胞因子、一氧化氮合酶和血脑屏障的影响
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Effects of Grape Seed Procyanidins on Cytokines,Nitric Oxide Synthase and Blood-Brain Barrier After Cerebral Ischemia-Reperfusion in Mice
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    目的探讨葡萄籽原花青素对缺血再灌注小鼠脑组织细胞因子、一氧化氮合酶和血脑屏障通透性的影响。方法采用夹闭小鼠双侧颈总动脉30 min再灌注72 h的脑缺血再灌注模型,并于双侧颈总动脉夹闭时及再灌注后每隔24 h分别腹腔注射蒸馏水、葡萄籽原花青素(10、20及40 mg/kg)和尼莫地平(2 mg/kg)。在处死动物前1 h经尾静脉注射2%伊文思蓝,采用ABC-ELISA法检测脑组织中白细胞介素1β和白细胞介素10含量,采用分光光度法检测脑组织中一氧化氮合酶活性及伊文思蓝含量。同时光镜观察小鼠海马CA1区脑组织的病理变化。结果与假手术组相比,缺血再灌注组脑组织中白细胞介素1β含量、一氧化氮合酶活性及伊文思蓝含量明显增高(p<0.01),而白细胞介素10含量降低,但无统计学意义。与缺血再灌注组相比,葡萄籽原花青素及尼莫地平治疗组脑组织中白细胞介素1β含量、一氧化氮合酶活性及伊文思蓝含量有不同程度的降低,而白细胞介素10含量有不同程度的升高。病理学组织检查发现,葡萄籽原花青素能改善脑缺血再灌注所造成的神经细胞损伤,减少神经细胞坏死。结论葡萄籽原花青素可能通过降低小鼠脑缺血再灌注时一氧化氮合酶活性和促炎因子白细胞介素1β含量,提高抗炎因子白细胞介素10含量进而降低血脑屏障的通透性而发挥脑保护作用。

    Abstract:

    Aim To investigate the effect of grape seed procyanidins on cytokines,nitric oxide synthase and blood-brain barrier and the pathological changes after cerebral ischemia-reperfusion in mice. Methods The incomplete cerebral ischemia-reperfusion mice models were induced by occlusion of both common carotid arteries for 30 min and reperfusion for 72 h.Distilled water,grape seed procyanidins(10,20 and 40 mg/kg) or Nimdipine(2 mg/kg) was injected intraperitoneally during the bilateral common carotid arteries occlusion and again at 24 h after reperfusion.An injection of 2% Evans blue into tail veins was conducted 1 h before the animals were sacrificed.The levels of interleukin-1β,nitric oxide synthase activities and content of Evans blue in the brain tissue were examined by ABC-ELISA method and spectrophotometry respectively.Meanwhile,the pathological changes of CA1 area of hippocampus were observed by light microscope. Results The levels of interleukin-1β,nitric oxide synthase activities and content of Evans blue in the brain tissue were significantly increased(p<0.01),but the levels of interleukin-10 were decreased compared with those in the sham surgery group.The levels of interleukin-1β,nitric oxide synthase activities and content of Evans blue in the brain tissue in the grape seed procyanidins or Nimdipine treated group had different decrease while the levels of interleukin-10 had different increase compared with those in the ischemia-reperfusion group.Pathological examination showed that grape seed procyanidins could significantly protect brain from ischemia-reperfusion injury,reduce the necrosis of neuron. Conclusion Grape seed procyanidins exerted an protective effect on the cerebral ischemic reperfused brain as evidenced by increasing the levels of anti-inflammatory cytokine such as interleukin-10 but reducing the levels of proinflammatory cytokine such as interleukin-1β,nitric oxide synthase activities as well as permeability of blood-brain barrier.

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吴秀香,卢晓梅,杜莉莉,金玉楠,张海鹏.原花青素对脑缺血再灌注小鼠脑组织细胞因子、一氧化氮合酶和血脑屏障的影响[J].中国动脉硬化杂志,2006,14(8):665~668.

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  • 收稿日期:2005-10-08
  • 最后修改日期:2006-07-12
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