INDUCTION OF ACUTE-PHASE GENE-EXPRESSION BY BRAIN IRRADIATION
INDUCTION OF ACUTE-PHASE GENE-EXPRESSION BY BRAIN IRRADIATION
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DOI：
10.1016/0360-3016(95)00279-8
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发表时间：
1995-10-15
影响因子：
7
通讯作者：
MCBRIDE, WH
中科院分区：
文献类型：
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作者：
HONG, JH;CHIANG, CS;MCBRIDE, WH
目的：为了研究脑的体内急性期分子反应，方法和材料：C3 Hf/Sed//Kam小鼠给予中脑或全身照射，脑内白细胞介素表达（IL-1 α、IL-1 β、IL-2、IL-3、IL-4、IL-5、IL-6）、干扰素（IFN-γ）、肿瘤坏死因子（TNF-α和TNF-β），细胞间粘附分子-1（ICAM-1），诱导型一氧化氮合成酶（iNOS），血管性血友病因子（vWF），用核糖核酸酶（RNase）保护试验测定不同辐射剂量后不同时间点α 1-抗糜蛋白酶（EB 22/5.3）和胶质细胞酸性蛋白（GFAP）的含量。地塞米松或喷替福林治疗小鼠对辐射诱导的基因expression.Results的影响：TNF-α，IL-1 β，ICAM-1，EB 22/5.3的水平，并在较小程度上IL-1 α和GFAP，信使RNA在照射后的大脑中增加，无论剂量被传递到全身或仅到中脑。反应是辐射剂量依赖性的，但没有发现低于7戈伊;例外的是ICAM-1，这是增加剂量低至2戈伊。大多数反应是快速的，在4-8小时内达到峰值，但抗胰凝乳蛋白酶和GFAP反应延迟，仍然。在24 h时升高，此时其他已消退。用地塞米松或喷替福林预处理小鼠可部分或完全抑制辐射诱导的基因表达。地塞米松是更多的抑制比penastrofylline在所选择的doses.Conclusions：最初的反应，大脑辐射涉及炎症基因产物的表达，这可能是负责临床观察到的早期症状的脑放疗。这种机制解释了在这种情况下临床使用类固醇的有益效果。
Purpose: To investigate the in vivo acute phase molecular response of the braiMethods and Materials: C3Hf/Sed//Kam mice were given midbrain or whole-body irradiation, Cerebral expression of interleukins (IL-1 alpha, IL-1 beta, IL-2, IL-3, IL-4, IL-5, IL-6), interferon (IFN-gamma), tumor necrosis factors (TNF-alpha and TNF-beta), intercellular adhesion molecule-1 (ICAM-1), inducible nitric oxide synthetase (iNOS), von Willebrand factor (vWF), alpha 1-antichymotrypsin (EB22/5.3), and glial fibrillary acidic protein (GFAP) was measured at various times after various radiation doses by ribonuclease (RNase) protection assay. The effects of dexamethasone or pentoxifylline treatment of mice on radiation-induced gene expression were also examined.Results: Levels of TNF-alpha, IL-1 beta, ICAM-1, EB22/5.3, and to a lesser extent IL-1 alpha and GFAP, messenger RNA were increased in the brain after irradiation, whether the dose was delivered to the whole body or only to the midbrain. Responses were radiation dose dependent, but were not found below 7 Gy; the exception being ICAM-1, which was increased by doses as low as 2 Gy. Most responses were rapid, peaking within 4-8 h, but antichymotrypsin and GFAP responses were delayed and still. elevated at 24 h, by which time the others had subsided. Pretreatment of mice with dexamethasone or pentoxifylline suppressed radiation-induced gene expression, either partially or completely. Dexamethasone was more inhibitory than pentoxifylline at the doses chosen.Conclusions: The initial response of the brain to irradiation involves expression of inflammatory gene products, which are probably responsible for clinically observed early symptoms of brain radiotherapy. This mechanism explains the beneficial effects of the clinical use of steroids in such circumstances.