Radiation attenuates physiological angiogenesis by differential expression of VEGF, Ang-1, tie-2 and Ang-2 in rat brain.

Radiation attenuates physiological angiogenesis by differential expression of VEGF, Ang-1, tie-2 and Ang-2 in rat brain.
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DOI:
10.1667/rr2647.1
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发表时间:
2011-12
期刊:
影响因子:
3.4
通讯作者:
Lee YW
Lee YW
中科院分区:
医学3区
文献类型:
--
作者:
Lee WH;Cho HJ;Sonntag WE;Lee YW

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放射性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大鼠接受单次10戈伊γ射线全脑照射或假照射,并在照射后4、8和24 h维持。采用免疫荧光双染法观察脑内EC增殖/凋亡情况。实时荧光定量RT-PCR和免疫荧光染色检测脑组织血管内皮生长因子(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,在照射大鼠脑中检测到CD 31免疫反应阳性细胞显着减少。全脑照射显著抑制EC增殖,增加EC凋亡。此外,VEGF,Ang-1和Tie-2的mRNA和蛋白表达的显着下降,观察到在照射大鼠脑。相反,全脑照射显著上调大鼠脑中Ang-2的表达。本研究提供了新的证据表明,全脑照射差异影响VEGF,Ang-1,Tie-2和Ang-2的mRNA和蛋白质表达。这些变化与脑内EC增殖减少和EC凋亡增加密切相关。
The etiology of radiation-induced cerebrovascular rare-faction 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 immunofluores-cence staining. A significant reduction in CD31-immunore-active 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.
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