中国神经再生研究(英文版) ›› 2014, Vol. 9 ›› Issue (11): 1154-1162.doi: 10.4103/1673-5374.135318

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

基质金属蛋白酶9高表达诱发自发性高血压模型大鼠脑梗死后微血管形成及基底膜损伤

  

  • 收稿日期:2014-04-18 出版日期:2014-06-12 发布日期:2014-06-12
  • 基金资助:

    中华医学会项目(No.82-143)

High matrix metalloproteinase-9 expression induces angiogenesis and basement membrane degradation in stroke-prone spontaneously hypertensive rats after cerebral infarction

  1. Department of Pathology, the First Affiliated Hospital of Medical School of Xi’an Jiaotong University, Xi’an, Shaanxi Province, China
  • Received:2014-04-18 Online:2014-06-12 Published:2014-06-12
  • Contact: Huilian Hou, Ph.D., Department of Pathology, the First Affiliated Hospital of Medical School of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China, hhlsnl@sina.com.
  • Supported by:

    This work was supported by the China Medical Board Project, No. 82-143.

摘要:

发生脑梗死后,其周围半暗区微血管基底膜成分降解,血脑屏障的完整性受到破坏,通透性增加,脑神经元及功能受到严重影响。未明确其具体诱发机制,实验以连续7周给予自发性高血压大鼠高浓度钠(1.3% NaCl)水溶液灌胃诱发脑梗死,通过免疫组化和免疫荧光检测,发现与发生脑梗死的自发性高血压大鼠非梗死侧(对侧)、摄入正常浓度钠(0.9% NaCl)水溶液自发性高血压大鼠及摄入不同浓度盐水的WKY大鼠相比,发生脑梗死的自发性高血压大鼠脑梗死周围半暗区中基质金属蛋白酶9高表达,Ⅳ型胶原阳性不连续血管数量与微血管密度均显著增加,Ⅳ型胶原阳性连续血管数量减少,且线性相关分析显示自发性高血压大鼠脑梗死后梗死半暗带中基质金属蛋白酶9表达与不连续Ⅳ型胶原阳性血管及微血管密度呈正相关。提示摄入高浓度钠引起局灶性脑梗死的自发性高血压大鼠,基质金属蛋白酶9高表达促进了微血管形成及基底膜主要成分Ⅳ型胶原的降解。

关键词: 神经再生, 脑梗死, 基质金属蛋白酶9, Ⅳ型胶原, 微血管密度, 血管生成, 基底膜损伤, 高钠, 自发性高血压

Abstract:

Basement membrane degradation and blood-brain barrier damage appear after cerebral infarction, severely impacting neuronal and brain functioning; however, the underlying pathogenetic mechanisms remain poorly understood. In this study, we induced cerebral infarction in stroke-prone spontaneously hypertensive rats by intragastric administration of high-sodium water (1.3% NaCl) for 7 consecutive weeks. Immunohistochemical and immunofluorescence assays demonstrated that, compared with the non-infarcted contralateral hemisphere, stroke-prone spontaneously hypertensive rats on normal sodium intake and Wistar-Kyoto rats, matrix metalloproteinase-9 expression, the number of blood vessels with discontinuous collagen IV expression and microvessel density were significantly higher, and the number of continuous collagen IV-positive blood vessels was lower in the infarct border zones of stroke-prone spontaneously hypertensive rats given high-sodium water. Linear correlation analysis showed matrix metalloproteinase-9 expression was positively correlated with the number of discontinuously collagen IV-labeled blood vessels and microvessel density in cerebral infarcts of stroke-prone spontaneously hypertensive rats. These results suggest that matrix metalloproteinase-9 upregulation is associated with increased regional angiogenesis and degradation of collagen IV, the major component of the basal lamina, in stroke-prone spontaneously hypertensive rats with high-sodium water-induced focal cerebral infarction.

Key words: nerve regeneration, cerebral infarction, matrix metalloproteinase-9, collagen IV, microvessel density, angiogenesis, basement membrane degradation, high sodium, stroke-prone spontaneously hypertensive, China Medical Board Project, neural regeneration