Long-term pathological and immunohistochemical features in the liver after intraoperative whole-liver irradiation in rats.

Long-term pathological and immunohistochemical features in the liver after intraoperative whole-liver irradiation in rats.
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DOI:
10.1093/jrr/rru005
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发表时间:
2014-07
影响因子:
2
通讯作者:
Nakano T
Nakano T
中科院分区:
医学4区
文献类型:
--
作者:
Imaeda M;Ishikawa H;Yoshida Y;Takahashi T;Ohkubo Y;Musha A;Komachi M;Nakazato Y;Nakano T

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放射治疗(RT)最近已成为特别重要的治疗肝肿瘤,但很少有关于放射性肝损伤的长期随访期间的实验研究。因此,本研究使用术中全肝照射模型检查了10个月期间的病理肝脏特征。在血液样品中进行肝功能试验,而在肝组织中进行病理学评价细胞死亡、细胞增殖和纤维化变化,所述肝组织是在给予0(对照)、15或30戈伊的单次照射剂量后24小时、1、2、4和40周从照射大鼠收集的。在15戈伊组中观察到的肝功能受损、肝细胞数量增加和凋亡细胞比例降低在40周后恢复至对照组水平,但在30戈伊组中未观察到;然而,15戈伊组的Ki-67指数在40周后仍高于对照组。Azan染色显示30戈伊照射组肝纤维化,但15和30戈伊照射组α-平滑肌肌动蛋白(α-SMA)和转化生长因子-β 1(TGF-β1)的表达水平均显著高于对照组(P < 0.05)。15戈伊和30戈伊照射组肝组织病理学特征存在差异,但TGF-β1和α-SMA表达模式支持两组放射性肝纤维化的渐进性进展。这些发现将有助于未来放射性肝损伤防护药物的开发。
Radiation therapy (RT) has become particularly important recently for treatment of liver tumors, but there are few experimental investigations pertaining to radiation-induced liver injuries over long-term follow-up periods. Thus, the present study examined pathological liver features over a 10-month period using an intraoperative whole-liver irradiation model. Liver function tests were performed in blood samples, whereas cell death, cell proliferation, and fibrotic changes were evaluated pathologically in liver tissues, which were collected from irradiated rats 24 h, 1, 2, 4 and 40 weeks following administration of single irradiation doses of 0 (control), 15 or 30 Gy. The impaired liver function, increased hepatocyte number, and decreased apoptotic cell proportion observed in the 15 Gy group, but not the 30 Gy group, returned to control group levels after 40 weeks; however, the Ki-67 indexes in the 15 Gy group were still higher than those in the control group after 40 weeks. Azan staining showed a fibrotic pattern in the irradiated liver in the 30 Gy group only, but the expression levels of alpha smooth muscle actin (α-SMA) and transforming growth factor-beta 1 (TGF-β1) in both the 15 and 30 Gy groups were significantly higher than those in the control group (P < 0.05). There were differences in the pathological features of the irradiated livers between the 15 Gy and 30 Gy groups, but TGF-β1 and α-SMA expression patterns supported the gradual progression of radiation-induced liver fibrosis in both groups. These findings will be useful in the future development of protective drugs for radiation-induced liver injury.
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