大鼠心脏组织TGF-β1 mRNA表达水平与放射性损伤关系的实验研究

背景与目的:放射性心脏损伤是影响接受纵隔放疗患者长期生存的预后因素之一,本研究探讨大鼠受照后心脏转化生长因子β1(transforming growth factorβ1,TGF-β1)mRNA水平随时间的变化及与放射性损伤发生发展的关系,为进一步抗纤维化药物治疗放射性心脏损伤的实验研究提供参考。方法:将60只大鼠分为两组。对照组大鼠不接受照射,受照组给予心脏照射20Gy,分别在受照后第1天、第2、4、8、12、24周每组解剖5只大鼠,检测血清肌钙蛋白和肌酸激酶同工酶(isoenzyme of creatine kinase,CK-MB)水平的变化,定量PCR检测心脏组织TGF-β1mRNA表达,并行心脏组织学切片评价心脏受照后损伤程度。结果:照射后24h实验组血清肌钙蛋白即有升高,2周时达到高峰(0.73±0.11)ng/mL],与对照组(0.11±0.04)ng/mL]相比差异有统计学意义(P<0.05);实验组CK-MB无明显变化,两组相比差异无统计学意义(P>0.05)。心脏TGF-β1mRNA表达在照射后第1天即出现升高,并在第2、12周出现高峰受照组为(8.55±1.19)×10-8μg/mL以及(4.63±0.41)×10-8μg/mL,对照组为(1.27±0.11)×10-8μg/mL以及(1.35±0.15)×10-8μg/mL],两组相比差异有统计学意义(P<0.05)。心脏受照后自第2周起纤维细胞比例增加受照组为(2.87±0.37)%,对照组为(1.14±0.55)%],随时间延长放射性损伤逐渐加重,两组相比差异有统计学意义(P<0.05);心肌组织纤维化程度的变化与TGF-β1mRNA表达水平的变化有显著的正相关性(P<0.05,r=0.48)。结论:TGF-β1参与心肌纤维化的形成。在TGF-β1分泌高峰期使用抗纤维化药物对其水平进行抑制,可能对组织纤维化形成产生预防作用。

Correlation of TGF-beta1 mRNA expression to irradiation-induced heart damage in rats

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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.