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低剂量放疗抗炎作用的时间进程:与转化生长因子-β1(TGF-β1)表达的相关性

Time course of anti-inflammatory effect of low-dose radiotherapy: correlation with TGF-beta(1) expression.

作者信息

Arenas Meritxell, Gil Fèlix, Gironella Meritxell, Hernández Víctor, Biete Albert, Piqué Josep M, Panés Julián

机构信息

Department of Radiation Oncology, Hospital Clínic de Barcelona, University of Barcelona, Spain.

出版信息

Radiother Oncol. 2008 Mar;86(3):399-406. doi: 10.1016/j.radonc.2007.10.032. Epub 2007 Nov 26.

DOI:10.1016/j.radonc.2007.10.032
PMID:18031855
Abstract

BACKGROUND AND PURPOSE

Low-dose radiotherapy (LD-RT) has a potent anti-inflammatory effect, and transforming growth factor (TGF)-beta(1) is a potential mediator of this effect. The objectives of this study were to characterize the in vivo effects of LD-RT on leukocyte recruitment over time, and its relationship with TGF-beta(1) production.

MATERIALS AND METHODS

Mice were submitted to abdominal irradiation with a dose of 0.3 Gy, or to sham radiation and studied 5, 24, 48 or 72 h after irradiation. Four hours before the study a proinflammatory stimulus consisting of LPS or placebo was administered. Leukocyte-endothelial cell interactions in intestinal venules were assessed using intravital microscopy. Circulating levels and intestinal tissue production of TGF-beta(1) were determined.

RESULTS

Compared to non-irradiated LPS-challenged group, the number of adherent leukocytes was significantly reduced 5, 24 and 48 h, but not 72 h after irradiation in LPS-challenged mice. Rolling leukocytes were significantly decreased at all time points analyzed. Plasma TGF-beta(1) levels were increased 5 and 24h after irradiation. Increased intestinal production during this period was corroborated by in vitro culture experiments.

CONCLUSIONS

LD-RT has a sustained inhibitory effect on leukocyte recruitment for 48 h, which is initially associated with an increase in TGF-beta(1) intestinal production.

摘要

背景与目的

低剂量放疗(LD-RT)具有强大的抗炎作用,转化生长因子(TGF)-β1是这种作用的潜在介质。本研究的目的是描述LD-RT随时间对白细胞募集的体内影响及其与TGF-β1产生的关系。

材料与方法

对小鼠进行0.3 Gy的腹部照射,或假照射,并在照射后5、24、48或72小时进行研究。在研究前4小时给予由脂多糖(LPS)或安慰剂组成的促炎刺激。使用活体显微镜评估肠小静脉中的白细胞-内皮细胞相互作用。测定循环水平和肠道组织中TGF-β1的产生。

结果

与未照射的LPS刺激组相比,在LPS刺激的小鼠中,照射后5、24和48小时,黏附白细胞的数量显著减少,但72小时时没有减少。在所有分析的时间点,滚动白细胞均显著减少。照射后5小时和24小时血浆TGF-β1水平升高。体外培养实验证实了在此期间肠道产生增加。

结论

LD-RT对白细胞募集有48小时的持续抑制作用,这最初与肠道TGF-β1产生增加有关。

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