Establishment of radiation-induced heart damage rat model and its early detection indicators
Feng Zhangxin1, Lu Bing2, Ouyang Weiwei2, Su Shengfa2, Zhang Dingwen3, Wang Wei4, Wan Yan1, Li Qingsong2, Geng Yichao2, Ma Zhu2, Cao Dongdong1, Fu Shimei1
1Teaching and Research Section of Oncology, Guizhou Medical University, Guiyang 550004, China; 2Department of Oncology, Guizhou Cancer Hospital, Affiliated Hospital of Guizhou Medical University, Guiyang 550004, China; 3Department of Medical Iconography, Guizhou Cancer Hospital, Guiyang 550004, China; 4Department of Clinical Laboratory, Guizhou Cancer Hospital, Guiyang 550004, China
Abstract：Objective To explore the establishment of radiation-induced heart damage (RIDH) SD rat models caused by irradiation of 15Gy/3f and the changes in early detection indicators, and evaluate the effect of irradiation combined with recombinant human endostatin (Endostar). Methods 75 adult male SD rats were randomly divided into the blank control group (C group), Endostar group (E group), 25Gy irradiation group (MHD25 group), 15Gy irradiation group (MHD15 group) and 15Gy irradiation combined with Endostar group (MHD15+E group), respectively. Blood sample was taken to measure the CK, CK-MB, LDH and CRP at 24h, 48h and 15d after corresponding interventions. After cardiac echocardiography at 1, 3 and 6 months, 5 rats in each group were randomly sacrificed and myocardial tissues were collected for HE and Masson staining. Two-way ANOVA was employed for statistical analysis. Results Compared with group C, myocardial fibrosis were observed in the MHD15 group at 6 months (P<0.05), which occurred later than that in the MHD25 group. Ejection fraction (EF) and fractional shortening (FS) were significantly decreased after 3 months in each irradiation group (all P<0.05), whereas the degree of decrease was similar among all groups (all P>0.05). The expression levels of myocardial enzymes and inflammatory cytokines did not significantly differ among different groups (all P>0.05). Conclusions In the early stage, exposure to 15Gy/3f irradiation can cause cardiac function damage in SD rat hearts, such as the reduction of EF and FS, and even lead to myocardial fibrosis in the late stage, which is delayed and less severe than high-dose irradiation. Irradiation combined with Endostar has no significant effect on radiation myocardial injury in rats.
Feng Zhangxin,Lu Bing,Ouyang Weiwei et al. Establishment of radiation-induced heart damage rat model and its early detection indicators[J]. Chinese Journal of Radiation Oncology, 2021, 30(6): 602-607.
[1] Donnellan E, Phelan D, McCarthy C P, et al. Radiation-induced heart disease:a practical guide to diagnosis and management[J]. Cleve Clin J Med, 2016, 83(12):914-922. DOI:10.3949/ccjm.83a.15104. [2] Davis M, Witteles RM. Radiation-induced heart disease:an under-recognized entity?[J]. Curr Treat Options Cardiovasc Med, 2014, 16(6):317.DOI:10.1007/s11936-014-0317-2. [3] Ma CX, Zhao XK, Li YD. New therapeutic insights into radiation-induced myocardial fibrosis[J]. Ther Adv Chronic Dis, 2019, 10:2040622319868383.DOI:10.1177/2040622319868383. [4] Steiner I. Pathology of radiation induced heart disease[J]. Rep Pract Oncol Radiother, 2020, 25(2):178-181.DOI:10.1016/j.rpor.2019.12.015. [5] Haque W, Verma V, Fakhreddine M, et al. Trends in cardiac mortality in patients with locally advanced non-small cell lung cancer[J]. Int J Radiat Oncol Biol Phys, 2018, 100(2):470-477.DOI:10.1016/j.ijrobp.2017.10.031. [6] Atkins KM, Rawal B, Williams CL, et al. Cardiac events after radiation therapy (RT) for Stage Ⅱ-Ⅲ non-small cell lung cancer (nsclc):analysis of 748 patients[J]. Int J Radiat Oncol Biol Phys, 2018, 102(3):S90-S91.DOI:10.1016/j.ijrobp.2018.06.236. [7] Spetz J, Moslehi J, Sarosiek K. Radiation-induced cardiovascular toxicity:mechanisms, prevention, and treatment[J]. Curr Treat Options Cardiovasc Med, 2018, 20(4):31.DOI:10.1007/s11936-018-0627-x. [8] Cuomo JR, Javaheri SP, Sharma GK, et al. How to prevent and manage radiation-induced coronary artery disease[J]. Heart, 2018, 104(20):1647-1653.DOI:10.1136/heartjnl-2017-312123. [9] Portaluri M, Petruzzelli MF, Tramacere F, et al. B-type natriuretic peptide plasma level in 5-year breast cancer survivors after radiotherapy[J]. Int J Radiat Biol, 2019, 95(2):201-206.DOI:10.1080/09553002.2019.1542183. [10] Walaszczyk A,Szotysek K, Jelonek K, et al. Heart irradiation reduces microvascular density and accumulation of HSPA1 in mice[J]. Strahlenther Onkol, 2018, 194(3):235-242. DOI:10.1007/s00066-017-1220-z. [11] Pudil R. Detection of radiation induced cardiotoxicity:Role of echocardiography and biomarkers[J]. Rep Pract Oncol Radiother, 2020,25(3):327-330.DOI:10.1016/j.rpor.2020.02.012. [12] 李晔雄. 放射肿瘤治疗学[M].5版. 中国协和医科大学出版社, 2018.Li YX. Radiation oncology[M]. 5th ed. Peking Union Medical College Press, 2018. [13] Sridharan V, Seawright JW, Antonawich FJ, et al. Late aDministration of a palladium lipoic acid complex (POLY-MVA) modifies cardiac mitochondria but not functional or structural manifestations of radiation-induced heart disease in a rat model[J]. Radiat Res, 2017, 187(3):361-366.DOI:10.1667/RR14643.1. [14] 万艳,欧阳伟炜,苏胜发,等. 放射联合重组人血管内皮抑制素致心肌纤维化的作用机制[J]. 中华放射肿瘤学杂志, 2020, 29(4):294-299. DOI:10.3760/cma.j.cn113030-20190911-00009. Wan Y, Ouyang WW, Su SF, et al. Mechanism of effects of radiation combined with recombinant human vascular endostatin on myocardial fibrosis[J]. Chin J Radiat Oncol, 2020, 29(4):294-299. DOI:10.3760/cma.j.cn113030-20190911-00009. [15] Wang J, Wu Y, Yuan F, et al. Chronic intermittent hypobaric hypoxia attenuates radiation induced heart damage in rats[J]. Life Sci, 2016, 160(1):57-63.DOI:10.1016/j.lfs.2016.07.002. [16] Sridharan V, Tripathi P, Aykin-Burns N, et al. A tocotrienol-enriched formulation protects against radiation-induced changes in cardiac mitochondria without modifying late cardiac function or structure[J]. Radiat Res, 2015, 183(3):357-366.DOI:10.1667/RR13915.1. [17] van der Veen SJ, Ghobadi G, de Boer RA, et al. ACE inhibition attenuates radiation-induced cardiopulmonary damage[J]. Radiother Oncol, 2015, 114(1):96-103.DOI:10.1016/j.radonc.2014.11.017. [18] Zhang YC, Li XM, Yu Z, et al. Efficacy of pEgr-1-endostatin combined with ionizing radiation on hypoxic conditions in nude mice bearing SKOV3 ovarian carcinoma[J]. Oncol Lett, 2017,13(3):1101-1108. DOI:10.3892/ol.2017.5559. [19] Ruge T, Carlsson AC, Jansson JH, et al. The association between circulating endostatin levels and incident myocardial infarction[J]. Scand Cardiovasc J, 2018, 52(6):315-319. DOI:10.1080/14017431.2018.1547839. [20] Pudil R. Detection of radiation induced cardiotoxicity:Role of echocardiography and biomarkers[J]. Rep Pract Oncol Radiother, 2020, 25(3):327-330.DOI:10.1016/j.rpor.2020.02.012. [21] Neuwirth R, Cvek J, Knybel L, et al. Stereotactic radiosurgery for ablation of ventricular tachycardia[J]. Europace, 2019, 21(7):1088-1095. DOI:10.1093/europace/euz133. [22] De Sanctis V, Alfò M, Vitiello C, et al. Markers of cardiotoxicity in early breast cancer patients treated with a hypofractionated schedule:a prospective study[J]. Clin Breast Cancer, 2020, 10:S1526-8209(20)30220-2. DOI:10.1016/j.clbc.2020.09.005. [23] Yeh C, Srichai B, Barac A, et al. A Prospective study assessing early cardiotoxicity after trimodality therapy for esophageal cancer[J]. Int J Radiat Oncol Biol Phys, 2018,102:S29. DOI:10.1016/j.ijrobp.2018.06.056. [24] Demissei BG, Freedman G, Feigenberg SJ, et al. Early changes in cardiovascular biomarkers with contemporary thoracic radiation therapy for breast cancer, lung cancer, and lymphoma[J]. Int J Radiat Oncol Biol Phys, 2019, 103(4):851-860.DOI:10.1016/j.ijrobp.2018.11.013. [25] Saiki H, Petersen IA, Scott CG, et al. Risk of heart failure with preserved ejection fraction in older women after contemporary radiotherapy for breast cancer[J]. Circulation, 2017, 135(15):1388-1396.DOI:10.1161/CIRCULATIONAHA.116.025434. [26] Tepekoylu C, Graber M, Hirsch J, et al. P5127Toll-Like receptor 3 mediates radiation induced calcific aortic valve disease[J]. European Heart Journal, 2018:24.DOI:10.1093/eurheartj/ehy566.P5127.
2021, Vol. 30 
