Liu Hui, Xiong Mai, Xia Yun-Fei, Cui Nian-Ji, Lu Ru-Biao, Deng Ling, Lin Yue-Hao, Rong Tie-Hua
State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, P.R. China.
Int J Radiat Oncol Biol Phys. 2009 Apr 1;73(5):1552-9. doi: 10.1016/j.ijrobp.2008.12.005.
To investigate whether the application of pentoxifylline (PTX) and tocopherol l (Vit. E) could modify the development of radiation-induced heart disease and downregulate the expression of transforming growth factor (TGF)-beta1mRNA in rats.
A total of 120 Sprague-Dawley rats were separated into four groups: control group, irradiated group, experimental group 1, and experiment group 2. Supplementation was started 3 days before irradiation; in experimental group 1, injection of PTX (15 mg/kg/d) and Vit. E (5.5 mg/kg/d) continued till the 12th week postirradiation, whereas in experimental group 2 it was continued until the 24th week postirradiation. All rats were administrated a single dose of 20 Gy irradiation to the heart except the control group. Histopathologic evaluation was performed at various time points (Days 1, 2, 4, 8, and 12 and 24th week) up to 24 weeks after irradiation. Changes of levels of TGF-beta1 mRNA expression were also investigated at the same time points using competitive polymerase chain reaction.
Compared with the irradiated group, levels of TGF-beta1 mRNA of the rat hearts were relatively low in the two experimental groups on the 12th week postirradiation. In experimental group 1, there was a rebound expression of TGF-beta1 mRNA on the 24th week postirradiation, whereas that of the experimental group 2 remained low (p < 0.05). The proportions of collagen fibers of the two experimental groups were lower than that of irradiated group (p < 0.05). A rebound could be observed in the experimental group 1.
PTX and Vit. E downregulated the expression of TGF-beta1 mRNA. The irradiated rat hearts showed a marked pathologic response to the drugs. The withdrawal of drugs in the 12th week postirradiation could cause rebound effects of the development of fibrosis.
研究己酮可可碱（PTX）和维生素E（Vit.E）的应用是否可改变大鼠放射性心脏病的发展，并下调转化生长因子（TGF）-β1mRNA的表达。
总共120只Sprague-Dawley大鼠被分为四组：对照组、照射组、实验组1和实验组2。在照射前3天开始补充；在实验组1中，PTX（15mg/kg/d）和Vit.E（5.5mg/kg/d）的注射持续至照射后第12周，而在实验组2中持续至照射后第24周。除对照组外，所有大鼠均接受单次20Gy的心脏照射。在照射后长达24周的不同时间点（第1、2、4、8、12天和第24周）进行组织病理学评估。同时使用竞争性聚合酶链反应研究TGF-β1mRNA表达水平的变化。
与照射组相比，两个实验组大鼠心脏的TGF-β1mRNA水平在照射后第12周相对较低。在实验组1中，照射后第24周TGF-β1mRNA出现反弹表达，而实验组2的仍保持较低水平（p<0.05）。两个实验组的胶原纤维比例均低于照射组（p<0.05）。实验组1可观察到反弹。
PTX和Vit.E下调了TGF-β1mRNA的表达。照射后的大鼠心脏对药物表现出明显的病理反应。照射后第12周停药可导致纤维化发展的反弹效应。
