Rat model of fractionated (2 Gy/day) 60 Gy irradiation of the liver: long-term effects
Rat model of fractionated (2 Gy/day) 60 Gy irradiation of the liver: long-term effects
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DOI：
10.1007/s00411-013-0468-7
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发表时间：
2013-08-01
影响因子：
1.7
通讯作者：
Moriconi, Federico
中科院分区：
文献类型：
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作者：
Rave-Fraenk, Margret;Malik, Ihtzaz Ahmed;Moriconi, Federico
肝脏被认为是对辐射敏感的器官。然而，在大鼠身上，高单次剂量照射(HDI)只显示出轻微的影响。到目前为止，在这种动物模型中分次照射(FI)的后果还没有被研究过。照射结束后3个月处死大鼠，分别接受选择性肝脏FI(总剂量60Gy2Gyd)或HDI25Gy2次照射。为了研究急性效应，HDI处理的大鼠在1-48h的几个时间点被额外处死。照射后3个月，FI和HDI处理的大鼠在肉眼可见的肝表面小“疤痕”以及在汇管区和肝实质内分布的中性粒细胞数量增加方面没有发现差异。此外，在门静脉周围也没有发现HE染色组织的变化或明显的纤维化迹象。在FI治疗的肝脏中胆管数量增加，但在HDI治疗的肝脏中没有发现差异。检测血清碱性磷酸酶(AP)、天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、γ-谷氨酰转移酶(GT)和乳酸脱氢酶(LDH)水平。AP仅在FI后显着升高，而HDI导致血清AST和LDH水平显着升高。逆转录-聚合酶链式反应(RT-PCR)检测基质金属蛋白酶-2、9、14及其抑制物TIMP-1、TIMP-2和TIMP-3在HDI后即刻表达上调，但在FI或HDI后3个月未见上调。总体而言，我们在FI和HDI后看到点状差异，并在肝脏表面弥漫性形成小疤痕。缺乏“暂时性凝块”的形成和单核巨噬细胞的募集可能是瘢痕形成的一种解释，即对辐射的不完全修复反应。
The liver is considered a radiosensitive organ. However, in rats, high single-dose irradiation (HDI) showed only mild effects. Consequences of fractionated irradiation (FI) in such an animal model have not been studied so far. Rats were exposed to selective liver FI (total dose 60 Gy, 2 Gy/day) or HDI (25 Gy) and were killed three months after the end of irradiation. To study acute effects, HDI-treated rats were additionally killed at several time points between 1 and 48 h. Three months after irradiation, no differences between FI and HDI treatment were found for macroscopically detectable small "scars" on the liver surface and for an increased number of neutrophil granulocytes distributed in the portal fields and through the liver parenchyma. As well, no changes in HE-stained tissues or clear signs of fibrosis were found around the portal vessels. Differences were seen for the number of bile ducts being increased in FI- but not in HDI-treated livers. Serum levels indicative of liver damage were determined for alkaline phosphatase (AP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltransferase (gamma GT) and lactate dehydrogenase (LDH). A significant increase of AP was detected only after FI while HDI led to the significant increases of AST and LDH serum levels. By performing RT-PCR, we detected up-regulation of matrix metalloproteinases, MMP-2, MMP-9, MMP-14, and of their inhibitors, TIMP-1, TIMP-2 and TIMP-3, shortly after HDI, but not at 3 month after FI or HDI. Overall, we saw punctual differences after FI and HDI, and a diffuse formation of small scars at the liver surface. Lack of "provisional clot"-formation and absence of recruitment of mononuclear phagocytes could be one explanation for scar formation as incomplete repair response to irradiation.