Identification of Proteins Indicating Radiation-induced Hepatic Toxicity in Cirrhotic Rats
Identification of Proteins Indicating Radiation-induced Hepatic Toxicity in Cirrhotic Rats
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DOI：
10.1269/jrr.09114
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发表时间：
2010-11-01
影响因子：
2
通讯作者：
Han, Kwang-Hyub
中科院分区：
文献类型：
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作者：
Chung, Sook In;Seong, Jinsil;Han, Kwang-Hyub
放射治疗（RT）已成为局部晚期肝细胞癌（HCC）的姑息治疗之一。然而，肝毒性是肝癌放射治疗的主要障碍。本研究的目的是鉴定指示辐射诱导的肝毒性的蛋白质，其可用作可能的生物标志物。用硫代乙酰胺（TAA）0.3g/L饮水诱导Wistar大鼠肝硬化9周。组织学观察肝硬化的发展。采用10戈伊单次封闭照射1/3肝脏，造成放射性肝损伤。为了找出共同表达的蛋白质，肝组织和血清进行了分析，采用双向电泳和四极杆飞行时间质谱。使用蛋白质印迹法验证鉴定的蛋白质。组织学检查显示肝硬化放射性肝纤维化程度加重。与细胞核抗原的增殖减少和凋亡增加有关。肝组织和血清的蛋白质组学分析鉴定了60种蛋白质，其在TAA单独组和TAA加辐射组之间的表达显示出显著变化。其中，肝素酶前体的增加和肝细胞生长因子的减少在肝组织和血清中普遍显示辐射后。肝纤维化在放射后增加。这些蛋白可能有助于检测和监测放射性肝损伤。
Radiation therapy (RT) has been emerging as one of the palliative treatments for locally advanced hepatocellular carcinoma (HCC). However, hepatic toxicity is a major obstacle in radiotherapy for HCC. The purpose of this study is to identify proteins indicating radiation-induced hepatic toxicity in cirrhotic rats, which can be used as possible biomarkers. Liver cirrhosis was induced in Wistar rats with thioacetamide (TAA) 0.3 g/L in drinking water for 9 weeks. The development of liver cirrhosis was observed histologically. Radiation hepatic injury was induced by treating 1/3 of the liver with 10 Gy single close radiation. To find out commonly expressed proteins, liver tissue and serum were analyzed using two-dimensional electrophoresis and quadrupole time of flight mass spectrometry. Identified proteins were validated using western blotting. Histological examination showed that the degree of hepatic fibrosis increased by radiation in liver cirrhosis. It was associated with a decrease in the proliferation of cell nuclear antigen and an increase of apoptosis. The proteomic analysis of liver tissue and serum identified 60 proteins which showed significant change in expression between the TAA-alone and TAA-plus-radiation groups. Among these, an increase of heparanase precursor and decrease of hepatocyte growth factor were shown commonly in liver tissue and serum following radiation. Hepatic fibrosis increased following radiation in cirrhotic rats. These proteins might be useful in detecting and monitoring radiation-induced hepatic injury.