Significance of miRNA-21 Expression in Rabbits with High-Dose Fractional Radiation Heart Injury
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摘要:
目的 建立良好、可靠、稳定的放射性心脏损伤（radiation-induced heart disease，RIHD）模型，初步确定miRNA-21在血浆中表达趋势。 方法 成年雄性健康新西兰兔27只，随机分为对照组3只和照射组24只，采用3%戊巴比妥钠（用量为0.8～1.0 ml/kg）耳缘静脉麻醉，通过CT定位扫描勾画左心室前壁作为照射靶区。采用直线加速器（Elekta precise），6 MV高能X线，5 Gy/F、2 F/W的照射方式，每隔3 d照射直到照射总剂量为30 Gy。对照组兔麻醉后给予佯装照射。于照射后第6、24、72 h及第1、2、4、8、24周，通过耳缘静脉采集血浆通过RT-PCR检测miRNA-21表达，取心脏组织通过HE染色检测心脏损伤情况。 结果 照射后心肌纤维之间炎性细胞浸润，以单核细胞为主，心肌细胞水肿明显、排列紊乱，心肌细胞核轻度固缩、染色加深，出现少量异型细胞核，符合心脏损伤模型病变。RT-PCR检测miR-21在各个时间点和Control组比较均有升高，差异有统计学意义（P < 0.05）；6 h、24 h、72 h、1周、2周、4周时间点随着照射时间的延长，miR-21表达不断递增，在4周达到最高表达；8周、24周时间点显示随着照射时间的延长，miR-21表达下降（ P < 0.05）。 结论 多次分剂量、大分割照射可以构建良好、可靠、稳定的RIHD阶梯模型，可以较好地模拟RIHD的发生、发展的演变过程。血浆中miR-21表达检测可以初步预测RIHD纤维化进展。 Abstract:Objective To establish a good, reliable, and stable radiation-induced heart disease （RIHD）model, and to determine the miRNA-21 expression trend in plasma. Methods 27 adult male healthy New Zealand rabbits were randomly divided into control group （3） and irradiation group （24）. After anesthetized with 3% pentobarbital sodium （a dose of 0.8-1.0 ml/kg）, the rabbits were scanned by CT to determine target area by sketch the front wall of the left ventricle for the irradiation. Linear accelerator （Elekta Precise）, 6 MV high-energy X-ray, 5 Gy/F, 2 F/W irradiation, every 3 days until the total dose is 30 Gy. Rabbits in the control group were given sham irradiation after anesthesia. At 6, 24, 72 hours and 1, 2, 4, 8, and 24 weeks after irradiation, plasma was collected from the marginal ear vein to detect the expression of miRNA-21 by RT-PCR, and the heart tissue was collected to examine heart damage by HE staining. Results The inflammatory cells infiltrated between myocardial fibers after irradiation were mainly mononuclear cells. The edema of myocardial cells was obvious and the arrangement was disordered. The nucleus of myocardial cells was slightly contracted and the staining darkened. A few heterotypic nuclei were present, which was consistent with cardiac injury model lesions. miR-21 detection by RT-PCR was elevated and statistically significant at each time point compared with the control group （P < 0.05）. With the irradiation time course at 6 h, 24 h, 72 h, 1 w, 2 w, and 4 w, respectively, miR-21 expression continued to increase gradually and reached the peak expression at 4 w; miR-21 expression decreased in 8 w and 24 w indicates expression was reducing with irradiation time （ P < 0.05）. Conclusion Multiple doses and large doses of irradiation can build a good, reliable, and stable RIHD ladder model, which can better simulate the evolution of the occurrence and development of RIHD. Detection of miR-21 expression in plasma can initially predict the progression of RIHD fibrosis. -
Key words:
- Radiation-induced /
- Heart disease /
- miR-21
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图 2 HE染色光镜图片 ×100
注：对照组：正常肺组织HE染色结果；6 h/24 h/72 h/1周/2周/4周/8周/24周：经过30 Gy照射6 h、24 h、72 h、1周、2周、4周、8周、24周肺组织HE染色结果。
Figure 2. HE stained light microscope picture ×100
表 1 各实验组相关因子miR-21水平比较[n = 3，（
${{\bar x}}\pm s$ ）]Table 1. Comparison of miR-21 levels of related factors in each experimental group[n = 3，（
${{\bar x}}\pm s$ ）]基因表达 对照组 6 h 24 h 72 h 1周 2周 4周 8周 24周 F P miRNA-21
相对表达1.002 ±
0.0815.080 ±
1.635*15.167 ±
4.905*31.684 ±
7.616*92.311 ±
25.109*169.641 ±
50.391*237.718 ±
74.150*77.984 ±
19.472*68.698 ±
13.822*17.24 0.046 与对照组比较，*P < 0.05。 
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