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首页> 外文期刊>Experimental Neurology >Ulinastatin protects brain against cerebral ischemia/reperfusion injury through inhibiting MMP-9 and alleviating loss of ZO-1 and occludin proteins in mice
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Ulinastatin protects brain against cerebral ischemia/reperfusion injury through inhibiting MMP-9 and alleviating loss of ZO-1 and occludin proteins in mice

机译:Ulinastatin通过抑制MMP-9和小鼠中的ZO-1和occludin蛋白质的损失来保护脑脑缺血/再灌注损伤免受脑缺血/再灌注损伤

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摘要

Background: The effects of Ulinastatin (UTI) on the blood-brain barrier (BBB) in the acute phase of cerebral ischemia/reperfusion (I/R) are not clear. This study was to investigate the potential protective effects of UTI on the BBB and the underlying mechanisms.& para;Methods: Male CD-1 mice were subjected to transient middle cerebral artery occlusion (tMCAO) and randomly assigned to four groups: Sham (sham-operated), tMCAO (tMCAO + 0.9% saline), UTI-L (tMCAO + UTI 1500 U/100 g) and UTI-H (tMCAO + UTI 3000 U/100 g) group. UTI was administered immediately after reperfusion in the UTI-L and UTI-H groups. At 24 h after reperfusion, the neurological deficit, brain water content, and infarct volume were determined. Western blot and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to examine the expression of matrix metalloproteinase (MMP)-9, Zonula occludens-1 (ZO-1) and occludin in ischemic cerebral cortex. The integrity of the BBB was assessed by the leakage of Evans blue. & para;& para;Results: Compared with tMCAO group, both UTI-L and UTI-H groups showed significantly (P 0.001) ameliorated the neurological deficit (2.00 +/- 0.71 and 1.60 +/- 0.55 vs. 4.60 +/- 0.55), lessened brain water content (82.99% +/- 0.21% and 82.05% +/- 0.59% vs. 84.28% +/- 0.0.57%) and decreased the infarct volume (38.52% +/- 1.72% and 24.78% +/- 1.20% vs. 49.48% +/- 1.93%). In addition, significantly (P 0.001) decreased expression of MMP-9 (0.48 0.06 and 0.37 +/- 0.05 vs.0.76 +/- 0.10 for protein and 2.88 +/- 0.23 and 2.17 +/- 0.16 vs. 3.90 +/- 0.24 for mRNA) and alleviated loss of ZO-1 (0.19 +/- 0.04 and 0.24 0.05 vs. 0.25 +/- 0.03) and occludin (0.74 +/- 0.08 and 0.87 +/- 0.07 vs. 0.94 +/- 0.06) proteins were observed in both UTI-L and UTI-H groups.& para;& para;Conclusion: UTI protects the brain against ischemic injury potentially via down-regulating the expression of MMP-9 and alleviating loss of ZO-1 and occludin proteins to restore the BBB permeability.
机译:背景:乌司汀(UTI)对脑缺血/再灌注(I / R)急性期血脑屏障(BBB)的影响尚不清楚。本研究是探讨UTI对BBB和潜在机制的潜在保护作用。&段;方法:对阳性CD-1小鼠进行瞬时中间脑动脉闭塞(TMCAO),随机分配到四组:假(假-operated),TMCAO(TMCAO + 0.9%盐水),UTI-L(TMCAO + UTI 1500 U / 100g)和UTI-H(TMCAO + UTI 3000 U / 100g)组。在再灌注到UTI-L和UTI-H组后立即施用UTI。在再灌注后24小时,确定神经缺陷,脑含水量和梗塞体积。用于检测缺血性脑皮层中基质金属蛋白酶(MMP)-9,ZO-1)和闭塞素的基质金属蛋白酶(MMP)-9,ZO-1)和闭塞蛋白的表达的表达。通过埃文斯蓝的泄漏来评估BBB的完整性。结果:结果:与TMCAO组相比,UTI-L和UTI-H组都显着显示出来(P <0.001)改善神经缺陷(2.00 +/- 0.71和1.60 +/- 0.55与4.60 + / - 0.55),减少脑含水量(82.99%+/- 0.21%和82.05%+/- 0.59%与84.28%+/- 0.0.57%)并降低梗塞体积(38.52%+/- 1.72%和24.78%+/- 1.20%与49.48%+/- 1.93%)。此外,显着(P <0.001)显着降低MMP-9的表达(0.48.06和0.37 +/- 0.05 Vs.0.76 +/- 0.10,2.88 +/- 0.23和2.17 +/- 0.16与3.90 + / - mRNA的0.24),缓解ZO-1(0.19 +/- 0.04和0.24 0.05 vs.0.25 +/- 0.03)和occludin(0.74 +/- 0.08和0.87 +/- 0.07和0.94 +/-在UTI-L和UTI-H组中观察到蛋白质。&para;&para;结论:UTI潜在地通过降低MMP-9的表达来保护大脑免受缺血性损伤,并减轻ZO-1的丧失Occludin蛋白恢复BBB渗透性。

著录项

  • 来源
    《Experimental Neurology》 |2018年第2018期|共7页
  • 作者单位

    Hebei Med Univ Hosp 2 Dept Neurol 215 West Heping Rd Shijiazhuang 050000 Hebei Peoples R China;

    Hebei Med Univ Hosp 2 Dept Neurol 215 West Heping Rd Shijiazhuang 050000 Hebei Peoples R China;

    Hebei Med Univ Hosp 2 Dept Neurol 215 West Heping Rd Shijiazhuang 050000 Hebei Peoples R China;

    Hebei Med Univ Hosp 2 Dept Neurol 215 West Heping Rd Shijiazhuang 050000 Hebei Peoples R China;

    Hebei Key Lab Vasc Homeostasis Shijiazhuang Hebei Peoples R China;

    Hebei Key Lab Vasc Homeostasis Shijiazhuang Hebei Peoples R China;

    Hebei Key Lab Vasc Homeostasis Shijiazhuang Hebei Peoples R China;

    Hebei Key Lab Vasc Homeostasis Shijiazhuang Hebei Peoples R China;

    Hebei Med Univ Hosp 2 Dept Neurol 215 West Heping Rd Shijiazhuang 050000 Hebei Peoples R China;

    Henan Prov Peoples Hosp Dept Intervent Treatment Zhengzhou Henan Peoples R China;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 神经病学;
  • 关键词

    Cerebral ischemia/reperfusion; Ulinastatin; Matrix metalloproteinase-9; Zonula occludens-1; Occludin;

    机译:脑缺血/再灌注;乌氏菌素;基质金属蛋白酶-9;Zonula Occludens-1;occludin;

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