Study on the effect 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。选择雄性SD大鼠272只,随机分为假手术组、模型组、葛根素注射液组和梓葛冻干粉针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、14 d给药后,取脑提取微血管,用RT-PCR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mRNA表达。结果表明,与模型组相比,再灌注4、7、14 d,梓葛冻干粉针16.40、32.70、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-9mRNA表达的升高(p<0.01);并促进微血管中Claudin-5、Occludin、ZO-1 mRNA表达(p<0.05)。说明梓葛冻干粉针通过抑制MMP-9基因表达,并促进Claudin-5、Occludin、ZO-1基因表达,进而保护和改善脑微血管通透性。Abstract: This paper investigated the protective effect of Zige lyophilized powder for injection against the microvascular permeability after cerebral ischemia-reperfusion injury of rats in the celebral microcirculation.272 male sprague-dawley rats were randomly divided into sham group, model group, puerarin injection group, three groups of Zige lyophilized powder.It made a cerebral ischemia-reperfusion model using the line in the left middle cerebral artery occlusion ( MCAO) of rats in ischemia for2 h and reperfusion for 1, 4, 7 and 14 d, the model of rats was established by intravenous injection of drugs. The expression of MMP-9, ZO-1, Occludin and Claudin-5 mRNA of the brain microvessel in the lateral ischemic cerebral cortex was detected by fluorescence quantitative PCR.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 mRNA level in microvessel of the lateral ischemic cerebral cortex ( p < 0.01) , and could increase claudin-5, occludin, zo-1 mRNA level ( p < 0.05) in the corresponding time. These results suggested that Zige lyophilized powder for injection could improve and protect the microvascular permeability by reducing MMP-9 and increasing claudin-5, occludin, zo-1 mRNA level.
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Keywords:
- Zige lyophilized powder for injection /
- Claudin-5 /
- Occludin /
- Zo-1 /
- MMP-9 /
- microvascular permeability
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[1] 尚远宏, 田金凤, 汪宏锦, 等.梓葛冻干粉针对脑微血管内皮细胞缺氧/复氧损伤的保护作用[J].食品工业科技, 2016, 37 (7) :358-373. [2] Del Zoppo G J, Mabuchi T.Cerebral microvessel responses to focal ischemia[J].Journal of Cerebral Blood Flow&Metabolism, 2003, 23 (8) :879-894.
[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] 尚远宏, 田金凤, 汪宏锦, 等.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机制研究[J].食品工业科技, 2016, 37 (24) :350-354. [8] 原欢欢, 张继芬, 王琴, 等.RP-HPLC测定梓葛冻干粉针中的药物含量及有关物质[J].中国药学杂志, 2011, 46 (16) :1276-1279. [9] 原欢欢.梓葛冻干粉针的研制及其初步安全性评价[D].西南大学, 2012. [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) :539-543. [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] 孙微.脑缺血—再灌注损伤时MMP-9的表达及银杏叶的干预作用[D].长春:吉林大学, 2006. [13] Rosenberg G, Estrada E, Dencoff J.Matrix metalloproteinases and TIMPs are associated with blood-brain barrier opening after reperfusion in rat brain[J].Stroke, 1998, 29 (10) :2189-2195.
[14] 雷立芳, 涂秋云, 资晓宏.依达拉奉对脑缺血再灌注大鼠血脑屏障通透性及MMP-9表达的影响[J].广东医学, 2008, 29 (7) :1128-1130. [15] 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. [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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