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瓜氨酸:一种用于定量和监测上皮辐射诱导的小肠损伤的生理标志物。

Citrulline: a physiologic marker enabling quantitation and monitoring of epithelial radiation-induced small bowel damage.

作者信息

Lutgens Ludy C H W, Deutz Nicolaas E P, Gueulette John, Cleutjens Jack P M, Berger Martijn P F, Wouters Bradly G, von Meyenfeldt Maarten F, Lambin Philippe

机构信息

MAASTRO, Department of Radiation Therapy and Oncology, University Hospital Maastricht/Maastricht University, Maastricht, The Netherlands.

出版信息

Int J Radiat Oncol Biol Phys. 2003 Nov 15;57(4):1067-74. doi: 10.1016/s0360-3016(03)00781-8.

DOI:10.1016/s0360-3016(03)00781-8
PMID:14575838
Abstract

PURPOSE

Small bowel irradiation results in epithelial cell loss and consequently impairs function and metabolism. We investigated whether citrulline, a metabolic end product of small bowel enterocytes, can be used for quantifying radiation-induced epithelial cell loss.

METHODS AND MATERIALS

NMRI mice were subjected to single-dose whole body irradiation (WBI). The time course of citrullinemia was assessed up to 11 days after WBI. A dose-response relationship was determined at 84 h after WBI. In addition, citrullinemia was correlated with morphologic parameters at this time point and used to calculate the dose-modifying factor (DMF) of glutamine and amifostine on acute small bowel radiation damage.

RESULTS

After WBI, a time- and dose-dependent decrease in plasma citrulline level was observed with a significant dose-response relationship at 84 h. At this time point, citrullinemia significantly correlated with jejunal crypt regeneration (p < 0.001) and epithelial surface lining (p = 0.001). A DMF of 1.0 and 1.5 was computed at the effective dose 50 (ED50) level for glutamine and amifostine, respectively.

CONCLUSIONS

Citrullinemia can be used to quantify acute small bowel epithelial radiation damage after single-dose WBI. Radiation-induced changes in citrullinemia are most pronounced at 3 1/2 to 4 days postirradiation. At this time point, citrullinemia correlates with morphologic endpoints for epithelial radiation damage.

摘要

目的

小肠辐射会导致上皮细胞损失,进而损害其功能和代谢。我们研究了小肠肠细胞的代谢终产物瓜氨酸是否可用于量化辐射诱导的上皮细胞损失。

方法和材料

将NMRI小鼠进行单剂量全身照射(WBI)。在WBI后长达11天的时间里评估瓜氨酸血症的时间进程。在WBI后84小时确定剂量反应关系。此外,在这个时间点将瓜氨酸血症与形态学参数相关联,并用于计算谷氨酰胺和氨磷汀对急性小肠辐射损伤的剂量修正因子(DMF)。

结果

WBI后,观察到血浆瓜氨酸水平呈时间和剂量依赖性下降,在84小时时有显著的剂量反应关系。在这个时间点,瓜氨酸血症与空肠隐窝再生(p < 0.001)和上皮表面衬里(p = 0.001)显著相关。谷氨酰胺和氨磷汀在有效剂量50(ED50)水平下的DMF分别计算为1.0和1.5。

结论

瓜氨酸血症可用于量化单剂量WBI后急性小肠上皮辐射损伤。辐射诱导的瓜氨酸血症变化在照射后3.5至4天最为明显。在这个时间点,瓜氨酸血症与上皮辐射损伤的形态学终点相关。

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