实验性脑出血后大鼠脑内血管生成和细胞外基质相关基因表达的时程变化。

Temporal profile of angiogenesis and expression of extracellular matrix-related genes in rat brains following experimental intracerebral hemorrhage.

机构信息

Department of Neurology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China.

The First Affiliated Hospital, Department of Neurology, Hengyang Medical School, University of South China, Hengyang, Hunan, P.R. China.

出版信息

Sci Prog. 2022 Jul-Sep;105(3):368504221115509. doi: 10.1177/00368504221115509.

DOI:10.1177/00368504221115509

PMID:35899308

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10450485/

Abstract

BACKGROUND

Angiogenesis is essential for the repair process after intracerebral hemorrhage (ICH).

METHODS

Given the importance of the extracellular matrix (ECM) in angiogenesis, we analysed the temporal profile of angiogenesis in rat brains on days 4, 7, and 21 after ICH. To this end, we compared the expression of ECM-related genes between ICH-induced and sham-operated groups using a complementary DNA (cDNA) array. We further measured protein expression using western blot and immunohistochemistry assays. Fluorescein isothiocyanate (FITC)-dextran was injected into the tail vein to examine the angioarchitecture in the perihematomal region.

RESULTS

Among the 88 ECM-related genes, we identified 42, 50, and 38 genes that were significantly upregulated on days 4, 7, and 21 after ICH, respectively ( < 0.05). Particularly, collagens, integrins, and matrix metalloproteinases (MMPs) were significantly increased on day 4 post-ICH and continued to increase at the other time points. Western blot and immunohistochemistry analyses showed a comparable trend in the upregulation of MMPs. Compared to the sham group, FITC-dextran labelling demonstrated decreased perfusion and increased vascular permeability in the perihematomal region in the ICH group. Doxycycline, an MMP inhibitor, significantly reduced angiogenesis ( < 0.05).

CONCLUSIONS

The results of this study indicate that MMPs are involved in modulating angiogenesis following ICH.

摘要

背景

血管生成对于脑内出血（ICH）后的修复过程至关重要。

方法

鉴于细胞外基质（ECM）在血管生成中的重要性，我们分析了ICH 后第 4、7 和 21 天大鼠脑内血管生成的时间进程。为此，我们使用 cDNA 芯片比较了 ICH 诱导组和假手术组之间与 ECM 相关的基因表达。我们进一步使用 Western blot 和免疫组化检测来测量蛋白表达。通过尾静脉注射荧光素异硫氰酸酯（FITC）-葡聚糖来检测血肿周围区域的血管结构。

结果

在 88 个 ECM 相关基因中，我们分别鉴定出在 ICH 后第 4、7 和 21 天显著上调的 42、50 和 38 个基因（<0.05）。特别是，胶原、整合素和基质金属蛋白酶（MMPs）在 ICH 后第 4 天显著增加，并在其他时间点继续增加。Western blot 和免疫组化分析显示 MMPs 的上调具有相似的趋势。与假手术组相比，FITC-葡聚糖标记显示 ICH 组血肿周围区域的灌注减少和血管通透性增加。MMP 抑制剂强力霉素显著减少了血管生成（<0.05）。