Institute of Integrative Medicine, Xiangya Hospital, Central South University, Changsha 410008, Hunan, PR China.
J Neurol Sci. 2012 Dec 15;323(1-2):141-6. doi: 10.1016/j.jns.2012.09.002. Epub 2012 Oct 6.
Spontaneous intracerebral hemorrhage (ICH) is one of the most severe types of stroke. Thrombin has been reported to participate in brain repair following ICH and play an important role in angiogenesis. Our previous studies have shown that ICH induces angiogenesis in damaged rat brain, accompanied by upregulation of expression of thrombospondin (TSP)-1 and TSP-2. The aim of the present study was to investigate whether the expression of TSP-1 and TSP-2 was regulated by thrombin in rat brain following ICH. A rat model of ICH was induced by injection of autologous blood into the right globus pallidus (GP). Hirudin, a thrombin specific inhibitor, or thrombin was injected into the GP. Immunohistochemistry, quantitative real-time reverse-transcription polymerase chain reaction (RT-PCR) and western blot assays were applied. Results showed that ICH induced an increase in the expression of TSP-1 mRNA and TSP-2 mRNA after ICH, whereas hirudin significantly inhibited the expression of TSPs mRNA after ICH (P<0.05). In contrast, sole thrombin treatment in normal rats induced strong expression of TSP-1 or TSP-2 in the blood vessels around the damaged brain region when compared with those without thrombin treatment. Western blot analysis data confirmed that the protein levels of TSPs were significantly increased when compared with those in the sham control group (P<0.01). These findings support that thrombin positively regulates the expression of TSP-1 and TSP-2 after ICH, which may be involved in modulating angiogenesis in injured brains following ICH.
自发性脑出血（ICH）是最严重的中风类型之一。已有报道称凝血酶参与 ICH 后的脑修复，并在血管生成中发挥重要作用。我们之前的研究表明，ICH 可诱导受损大鼠脑中的血管生成，同时上调血小板反应蛋白（TSP）-1 和 TSP-2 的表达。本研究旨在探讨 ICH 后凝血酶是否调节大鼠脑内 TSP-1 和 TSP-2 的表达。通过将自体血注入右侧苍白球（GP）诱导大鼠 ICH 模型。将凝血酶特异性抑制剂水蛭素或凝血酶注入 GP。应用免疫组织化学、实时定量 RT-PCR 和 Western blot 检测。结果表明，ICH 后 TSP-1mRNA 和 TSP-2mRNA 的表达增加，而水蛭素明显抑制 ICH 后 TSPs mRNA 的表达（P<0.05）。相反，与未用凝血酶治疗的大鼠相比，单独用凝血酶处理正常大鼠可在损伤脑区周围的血管中强烈诱导 TSP-1 或 TSP-2 的表达。Western blot 分析数据证实，TSP 的蛋白水平与假手术对照组相比明显增加（P<0.01）。这些发现支持凝血酶在 ICH 后积极调节 TSP-1 和 TSP-2 的表达，这可能参与调节 ICH 后受损大脑中的血管生成。
