Liu Hui, Xiong Mai, Rong Tie-Hua, Cui Nian-Ji, Xia Yun-Fei, Deng Ling, Lin Yue-Hao
State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, PR China.
Ai Zheng. 2008 Jan;27(1):18-24.
BACKGROUND & OBJECTIVE: Radiation-induced heart damage is one of the prognostic factors of the patients who had received radiation to the mediastinum. This study was to investigate the correlation of transforming growth factor-beta1 (TGF-beta1) mRNA expression to the radiation response of the heart in rats, in order to provide references for further study on irradiation-induced heart damage.
Sixty Sprague-Dawley rats were divided into 2 groups: the 30 rats in irradiation group were irradiated with 20 Gy on the heart; the 30 rats in control group received no irradiation. At each time point of the 1st day, the 2nd, 4th, 8th 12th, and 24th week after irradiation, 5 rats in each group were killed. The serum levels of cardiac troponin and isoenzyme of creatine kinase (CK-MB) were detected. The expression of TGF-beta1 mRNA was detected by polymerase chain reaction (PCR). Heart damage was observed with Masson staining under microscope.
The serum level of cardiac troponin was elevated at 24 h after irradiation, and reached the peak at 2 weeks after irradiation, which was significantly higher than that in control group [(0.73+/-0.11) ng/mL vs. (0.11+/-0.04) ng/mL, P<0.05]. There was no significant difference in the serum level of CK-MB between two groups (P>0.05). The expression of TGF-beta1 mRNA was elevated at the 1st day after irradiation, and reached peaks at 2 and 12 weeks after irradiation, which were significantly higher than those in control group [(8.55+/-1.19)x10(-8) microg/mL vs. (1.27+/-0.11)x10(-8) microg/mL, (4.63+/-0.41)x10(-8) microg/mL vs. (1.35+/-0.15)x10(-8) microg/mL, P<0.05]. The proportion of collagen fibers was increased since 2 weeks after irradiation, which was significantly higher than that in control group [(2.87+/-0.37)% vs. (1.14+/-0.55)%, P<0.05]. The expression of TGF-beta1 mRNA was positively correlated to the proportion of collagen fibers in the rat hearts after irradiation (r=0.48, P<0.05).
TGF-beta1 is involved not only in the onset but also in the development of radiation fibrosis. Inhibiting the peak expression of TGF-beta1 mRNA may reduce the radiation-induced damage to the heart.
放射性心脏损伤是纵隔放疗患者的预后因素之一。本研究旨在探讨转化生长因子β1（TGF-β1）mRNA表达与大鼠心脏放射反应的相关性，为进一步研究放射性心脏损伤提供参考。
将60只Sprague-Dawley大鼠分为2组：照射组30只大鼠心脏接受20 Gy照射；对照组30只大鼠不接受照射。在照射后第1天、第2、4、8、12和24周的每个时间点，每组处死5只大鼠。检测血清心肌肌钙蛋白和肌酸激酶同工酶（CK-MB）水平。采用聚合酶链反应（PCR）检测TGF-β1 mRNA的表达。通过Masson染色在显微镜下观察心脏损伤情况。
照射后24 h血清心肌肌钙蛋白水平升高，照射后2周达到峰值，显著高于对照组[（0.73±0.11）ng/mL对（0.11±0.04）ng/mL，P<0.05]。两组血清CK-MB水平差异无统计学意义（P>0.05）。照射后第1天TGF-β1 mRNA表达升高，照射后2周和12周达到峰值，显著高于对照组[（8.55±1.19）×10^(-8) μg/mL对（1.27±0.11）×10^(-8) μg/mL，（4.63±0.41）×10^(-8) μg/mL对（1.35±0.15）×10^(-8) μg/mL，P<0.05]。照射后2周起胶原纤维比例增加，显著高于对照组[（2.87±0.37）%对（1.14±0.55）%，P<0.05]。照射后大鼠心脏中TGF-β1 mRNA表达与胶原纤维比例呈正相关（r=0.48，P<0.05）。
TGF-β1不仅参与放射性纤维化的发生，还参与其发展。抑制TGF-β1 mRNA的峰值表达可能减轻放射性心脏损伤。
