Institute of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
J Neurosurg. 2012 Nov;117(5):920-8. doi: 10.3171/2012.8.JNS112152. Epub 2012 Sep 7.
Angiogenesis occurs after intracerebral hemorrhage (ICH). Thrombin mediates mitogenesis and survival in endothelial cells and induces angiogenesis. The present study aimed to clarify whether thrombin is involved in triggering ICH-related angiogenesis.
In the first part of the experiment, autologous blood (with or without hirudin) was injected to induce ICH. In the second part, rats received either 1 U (50 μl) thrombin or 50 μl 0.9% sterile saline. In both parts, 5-bromo-2-deoxyuridine (BrdU) was administered intraperitoneally. Brains were perfused to identify BrdU-positive/von Willebrand factor (vWF)-positive nuclei. The expression of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1) and Ang-2 was evaluated by immunohistochemistry and quantitative real-time reverse transcription polymerase chain reaction.
After ICH, the number of BrdU-/vWF-positive nuclei increased until Day 14, and vessels positive for HIF-1α, VEGF, Ang-1, and Ang-2 were observed around the clot. Quantitative analysis showed that ICH upregulated expression of HIF-1α, VEGF, Ang-1, and Ang-2 notably compared with that in sham controls (p < 0.05). However, hirudin significantly inhibited these effects. After thrombin treatment, many BrdU-positive/vWF-positive nuclei and HIF-1α-, VEGF-, Ang-1- and Ang-2-positive vessels could be detected around the affected region.
Thrombin can induce angiogenesis in rat brains and may be an important trigger for ICH-related angiogenesis.
脑出血（ICH）后会发生血管生成。凝血酶在血管内皮细胞中介导有丝分裂和存活，并诱导血管生成。本研究旨在阐明凝血酶是否参与触发与 ICH 相关的血管生成。
在实验的第一部分，自体血液（带或不带水蛭素）被注射以诱导 ICH。在第二部分，大鼠接受 1U（50μl）凝血酶或 50μl 0.9%无菌生理盐水。在两部分中，均经腹腔内给予 5-溴-2-脱氧尿苷（BrdU）。通过灌注大脑来鉴定 BrdU+/血管性血友病因子（vWF）+核。通过免疫组织化学和定量实时逆转录聚合酶链反应评估缺氧诱导因子-1α（HIF-1α）、血管内皮生长因子（VEGF）、血管生成素-1（Ang-1）和 Ang-2 的表达。
ICH 后，BrdU-/vWF+核的数量增加至第 14 天，并且在凝块周围观察到 HIF-1α、VEGF、Ang-1 和 Ang-2 阳性的血管。定量分析表明，与 sham 对照组相比，ICH 显著上调 HIF-1α、VEGF、Ang-1 和 Ang-2 的表达（p<0.05）。然而，水蛭素显著抑制了这些效应。在凝血酶处理后，在受影响区域周围可以检测到许多 BrdU+ / vWF+核和 HIF-1α、VEGF、Ang-1 和 Ang-2 阳性的血管。
凝血酶可诱导大鼠脑内血管生成，可能是与 ICH 相关的血管生成的重要触发因素。
