School of Biomedical Engineering and Sciences, Virginia Tech, Blacksburg, Virginia 24061, USA.
Radiat Res. 2011 Dec;176(6):753-60. doi: 10.1667/rr2647.1. Epub 2011 Sep 30.
The etiology of radiation-induced cerebrovascular rarefaction remains unknown. In the present study, we examined the effect of whole-brain irradiation on endothelial cell (EC) proliferation/apoptosis and expression of various angiogenic factors in rat brain. F344 × BN rats received either whole-brain irradiation (a single dose of 10 Gy γ rays) or sham irradiation and were maintained for 4, 8 and 24 h after irradiation. Double immunofluorescence staining was employed to visualize EC proliferation/apoptosis in brain. The mRNA and protein expression levels of vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1), endothelial-specific receptor tyrosine kinase (Tie-2), and Ang-2 in brain were determined by real-time RT-PCR and immunofluorescence staining. A significant reduction in CD31-immunoreactive cells was detected in irradiated rat brains compared with sham-irradiated controls. Whole-brain irradiation significantly suppressed EC proliferation and increased EC apoptosis. In addition, a significant decrease in mRNA and protein expression of VEGF, Ang-1 and Tie-2 was observed in irradiated rat brains. In contrast, whole-brain irradiation significantly upregulated Ang-2 expression in rat brains. The present study provides novel evidence that whole-brain irradiation differentially affects mRNA and protein expression of VEGF, Ang-1, Tie-2 and Ang-2. These changes are closely associated with decreased EC proliferation and increased EC apoptosis in brain.
辐射诱导的脑血管稀疏的病因尚不清楚。在本研究中,我们研究了全脑照射对大鼠脑内皮细胞(EC)增殖/凋亡和各种血管生成因子表达的影响。F344×BN 大鼠接受全脑照射(单次 10Gyγ射线)或假照射,并在照射后 4、8 和 24 小时进行维持。采用双重免疫荧光染色来观察脑内 EC 的增殖/凋亡。通过实时 RT-PCR 和免疫荧光染色测定脑内血管内皮生长因子(VEGF)、血管生成素-1(Ang-1)、内皮特异性受体酪氨酸激酶(Tie-2)和 Ang-2 的 mRNA 和蛋白表达水平。与假照射对照组相比,照射大鼠脑内 CD31 免疫反应性细胞明显减少。全脑照射显著抑制 EC 增殖并增加 EC 凋亡。此外,在照射大鼠脑内观察到 VEGF、Ang-1 和 Tie-2 的 mRNA 和蛋白表达显著降低。相比之下,全脑照射显著上调了大鼠脑内 Ang-2 的表达。本研究提供了新的证据,表明全脑照射对 VEGF、Ang-1、Tie-2 和 Ang-2 的 mRNA 和蛋白表达有不同的影响。这些变化与脑内 EC 增殖减少和凋亡增加密切相关。