Study on the effects and underling mechanism of Zige lyophilized powder for injection against the microvascular permeability after cerebral ischemia-reperfusion injury of rats in the celebral microcirculation
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摘要: 本文探讨梓葛冻干粉针对脑缺血/再灌注损伤大鼠脑微血管通透性的影响及其作用机制。选择雄性SD大鼠320只,随机分为假手术组、模型组、葛根素注射液组、尼莫地平组和梓葛冻干粉针3个剂量组。线栓法复制大鼠缺血再灌注模型,分别缺血2 h,于再灌注1、4、7和14 d给药后,取脑提取微血管,分别用Western blot法测定脑微血管中闭合蛋白（Occludin）、紧密连接蛋白-5（Claudin-5）、闭合小带蛋白-1（ZO-1）、基质金属蛋白酶-9（MMP-9）的蛋白表达。结果表明,与模型组相比,再灌注4、7和14 d,梓葛冻干粉针16.40、32.70和65.40 mg·kg-1能抑制脑缺血/再灌注大鼠缺血侧脑皮质层微血管中MMP-9蛋白表达的升高;并促进微血管中Claudin-5、Occludin、ZO-1蛋白表达。说明梓葛冻干粉针影响脑缺血/再灌注损伤大鼠脑微血管通透性的机制可能是通过抑制MMP-9蛋白表达,并促进Claudin-5、Occludin、ZO-1蛋白表达,进而保护和改善脑微血管通透性。Abstract: This paper investigated the possible mechanism underlying the protective effect of Zige lyophilized powder for injection against the microvascular permeability after cerebral ischemia- reperfusion injury of rats in the celebral microcirculation.320 male Sprague- Dawley rats were randomly divided into sham group,model group,puerarin injection group,nimodipine injection group,three groups of Zige lyophilized powder.Middle cerebral artery occlusion( MCAO) model was produced by using an intraluminal filament technique in rats. Drugs were administered intravenously( i.v.) 2 h after MCAO and reperfusion for 1,4,7 and 14 d.The expression levels of MMP-9,ZO- 1,Occludin and Claudin- 5 protein of the brain microvessel in the lateral ischemic cerebral cortex were detected by Western blot. In reperfusion for 4,7 and 14 d,compared with model group,Zige lyophilized powder groups( 16.40,32.70 and 65.40 mg·kg- 1) could reduce MMP-9 protein expression in microvessel of the lateral ischemic cerebral cortex,and could increase ZO- 1,Occludin and Claudin- 5 protein expression in the corresponding time.These results suggested that the protective effect of Zige lyophilized powder for injection on the microvascular permeability after cerebral ischemia- reperfusion injury was mediated by reducing MMP-9 and increasing ZO-1,Occludin,Claudin-5 protein expression.
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[1] 王光胜,耿德勤.脑缺血/再灌注损伤机制研究进展[J].医学综述,2011,17(24):3753-3756. [2] 孟淑静,曹春蕊,任艳焕,等.血管通透性及其相关因素研究进展[J].实用心脑肺血管病杂志,2011,19(10):1814-1815. [3] Jiao H,Wang Z,Liu Y,et al.Specific role of tight junction proteins claudin-5,occludin,and ZO-1 of the blood-brain barrier in a focal cerebral ischemic insult[J].Journal of Molecular Neuroscience,2011,44(2):130-139.
[4] Lapierre L A.The molecular structure of the tight junction[J].Advanced Drug Delivery Reviews,2000,41(3):255-264.
[5] Wang G,Guo Q,Hossain M,et al.Bone marrow-derived cells are the major source of MMP-9 contributing to blood-brain barrier dysfunction and infarct formation after ischemic stroke in mice[J].Brain Research,2009,1294:183-192.
[6] Yang Y,Estrada E Y,Thompson J F,et al.Matrix metalloproteinase-mediated disruption of tight junction proteins in cerebral vessels is reversed by synthetic matrix metalloproteinase inhibitor in focal ischemia in rat[J].Journal of Cerebral Blood Flow&Metabolism,2007,27(4):697-709.
[7] 邓礼娟,王琴,原欢欢,等.梓葛冻干粉针对气虚血瘀证大鼠凝血功能、血液流变学和NO的影响[J].中国中药杂志,2012,37(10):1472-1476. [8] 王琴.梓葛冻干粉针的药代动力学及改善血脑屏障通透性的机制研究[D].重庆:西南大学,2012. [9] 尚远宏,田金凤,汪宏锦,等.梓葛冻干粉针对大鼠急性脑微循环障碍的改善作用[J].中国中药杂志,2014,39(4):733-738. [10] 尚远宏,田金凤,李松青,等.不同缺血时间对脑缺血/再灌注损伤大鼠神经行为学的影响[J].西南民族大学学报:自然科学版,2015,41(5):539-43. [11] Hawkins B T,Abbruscato T J,Egleton R D,et al.Nicotine increases in vivo blood-brain barrier permeability and alters cerebral microvascular tight junction protein distribution[J].Brain Research,2004,1027(1):48-58.
[12] 袁毅,雷立芳,涂秋云,等.大鼠脑缺血再灌注中血脑屏障通透性的改变与基质金属蛋白酶9表达的关系[J].中国动脉硬化杂志,2008,16(7):510-512. [13] Lohmann C,Krischke M,Wegener J,et al.Tyrosine phosphatase inhibition induces loss of blood-brain barrier integrity by matrix metalloproteinase-dependent and-independent pathways[J].Brain Research,2004,995(2):184-196.
[14] 王静云,王国峰,赵仁亮.脑缺血预处理对脑缺血再灌注大鼠血脑屏障通透性和基质金属蛋白酶-9表达的影响[J].国际脑血管病杂志,2010,18(9):668-673. [15] 尚远宏.梓葛冻干粉针对大鼠脑微循环障碍的改善作用及其机制研究[D].重庆:西南大学,2014. [16] 李向红.脑缺血的微血管改变[J].微循环学杂志,1997,7(1):13-13. [17] 王静娥,田国萍,周进,等.大鼠脑缺血时紧密连接相关蛋白occludin和cllaudin-5表达的变化[J].解剖科学进展,2010,16(2):149-152.
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