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Establishment and validation of radiation-induced heart fibrosis on SD rat model
Yao Ye,Chen Jing,Li Zhenzhen,Li Xin,Chen Jing,Yang Hongjuan,Zhong Yahua,Xie Conghua
Department of Radiation Oncology and Medical Oncology,Zhongnan Hospital ofWuhan University,Hubei Cancer Clinical Study Center,Hubei Key Laboratory of Tumor Biological Behaviors,Wuhan 430071,China
AbstractObjective To establish a Sprague-Dawley (SD) rat model of radiation-induced heart injury and myocardial fibrosis. Methods Using the small animal radiation research platform,18-Gy radiation was given to the heart of male SD rats in a single fraction. At six months after radiation,heart structure and function were assessed by color Doppler ultrasound;heart injury and collagen fiber deposition were evaluated using HE staining and picrosirius red staining,respectively;heart collagen content was analyzed by hydroxyproline measurement. Results According to the color Doppler ultrasound assessment,the left ventricular posterior wall thickness during systole was significantly smaller in the radiation group than in the control group (0.22±0.01 vs. 0.25±0.05 cm,P=0.037).The results of picrosirius red staining showed that the proportions of fibrosis area in the right ventricle,interventricular septum,and left ventricle were significantly higher in the radiation group than in the control group ((2.99±1.29)% vs. (2.21±0.87)%,P=0.025;(2.53±1.27)% vs. (0.91±0.70)%,P=0.000;(2.45±1.98)% vs. (0.54±0.31)%,P=0.000). According to the measurement of hydroxyproline concentration,the radiation group had a significantly higher level of hydroxyproline than the control group (0.56±0.02 vs. 0.49±0.05 ug/mg,P=0.010),indicating severe heart collagen deposition after radiation. Conclusions At the end of model establishment,SD rats have obvious myocardial fibrosis and reduced left ventricular posterior wall thickness during systole,suggesting that a SD rat model of radiation-induced heart injury and myocardial fibrosis is successfully established.
Yao Ye,Chen Jing,Li Zhenzhen et al. Establishment and validation of radiation-induced heart fibrosis on SD rat model[J]. Chinese Journal of Radiation Oncology, 2017, 26(1): 84-89.
Yao Ye,Chen Jing,Li Zhenzhen et al. Establishment and validation of radiation-induced heart fibrosis on SD rat model[J]. Chinese Journal of Radiation Oncology, 2017, 26(1): 84-89.
[1] Baker JE,Moulder JE,Hopewell JW.Radiation as a risk factor for cardiovascular disease[J].Antioxid Redox Signal,2011,15(7):1945-1956.DOI:10.1089/ars.2010.3742. [2] Lancellotti P,Nkomo VT,Badano LP,et al. Expert consensus for multi-modality imaging evaluation of cardiovascular complications of radiotherapy in adults:a report from the European association of cardiovascular imaging and the American society of echocardiography[J].J Am Soc Echocardiogr,2013,26(9):1013-1032.DOI:10.1016/j.echo.2013.07.005. [3] Boerma M.Experimental radiation-induced heart disease:past,present,and future[J].Radiat Res,2012,178(1):1-6.DOI:10.1667/RR2933.1. [4] Filopei J,Frishman W.Radiation-inducedheartdisease[J].Cardiol Rev,2012,20(4):184-188.DOI:10.1097/CRD.0b013e3182431c23. [5] Prosnitz RG,Marks LB.Radiation-induced heart disease:vigilance is still required[J].J Clin Oncol,2005,23(30):7391-7394.DOI:10.1200/JCO.2005.07.011. [6] Schultz-Hector S,Trott KR.Radiation-induced cardiovascular diseases:is the epidemiologic evidence compatible with the radiobiologic data?[J].Int J Radiat Oncol Biol Phys,2007,67(1):10-18.DOI:10.1016/j.ijrobp.2006.08.071. [7] 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. [8] Boerma M,Hauer-Jensen M.Potential targets for intervention in radiation-induced heart disease[J].Curr Drμg Targets,2010,11(11):1405-1412.DOI:10.2174/1389450111009011405. [9] Ramyar A,Shafiei M,Moazzami K,et al. Severe valvular toxicity and pericarditis early after radiation therapy in a patient treated for Hodgkin's lymphoma[J].Turk J Pediatr,2010,52(4):423-425. [10] Berry GJ,Jorden M.Pathology of radiation and anthracycline cardiotoxicity[J].Pediatr Blood Cancer,2005,44(7):630-637.DOI:10.1002/pbc.20346. [11] Wong J,Armour E,Kazanzides P,et al. High-resolution,small animal radiation research platform with x-ray tomographic guidance capabilities[J].Int J Radiat Oncol Biol Phys,2008,71(5):1591-1599.DOI:10.1016/j.ijrobp.2008.04.025. [12] Sridharan V,Aykin-Burns N,Tripathi P,et al. Radiation-induced alterations in mitochondria of the rat heart[J].Radiat Res,2014,181(3):324-334.DOI:10.1667/RR13452.1. [13] Fajardo LF,Stewart JR.Experimental radiation-induced heart disease. I.Light microscopic studies[J].Am J Pathol,1970,59(2):299-316. [14] McChesney SL,Gillette EL,Powers BE.Radiation-induced cardiomyopathy in the dog[J].Radiat Res,1988,113(1):120-132.DOI:10.2307/3577185. [15] Barjaktarovic Z,Shyla A,Azimzadeh O,et al. Ionising radiation induces persistent alterations in the cardiac mitochondrial function of C57BL/6 mice 40 weeks after local heart exposure[J].Radiother Oncol,2013,106(3):404-410.DOI:10.1016/j.radonc.2013.01.017. [16] Boerma M,Hauer-Jensen M.Preclinical research into basic mechanisms of radiation-induced heart disease[J].Cardiol Res Pract,2011,2011:858262.DOI:10.4061/2011/858262. [17] Boerma M,Wang JR,Wondergem J,et al. Influence of mast cells on structural and functional manifestations of radiation-induced heart disease[J].Cancer Res,2005,65(8):3100-3107.DOI:10.1158/0008-5472.CAN-04-4333. [18] Sharma S,Moros EG,Boerma M,et al. A novel technique for image-guided local heart irradiation in the rat[J].Technol Cancer Res Treat,2014,13(6):593-603.DOI:10.7785/tcrtexpress.2013.600256. [19] Sridharan V,Tripathi P,Sharma S,et al. Roles of sensory nerves in the regulation of radiation-induced structural and functional changes in the heart[J].Int J Radiat Oncol Biol Phys,2014,88(1):167-174.DOI:10.1016/j.ijrobp.2013.10.014. [20] Hoving S,Seemann I,Visser NL,et al. Thalidomide is not able to inhibit radiation-induced heart disease[J].Int J Radiat Biol,2013,89(9):685-691.DOI:10.3109/09553002.2013.788797. [21] Boerma M,Wang JR,Kulkarni A,et al. Influence of endothelin 1 receptor inhibition on functional,structural and molecular changes in the rat heart after irradiation[J].Radiat Res,2008,170(3):275-283.DOI:10.1667/RR1093.1. [22] Boerma M,Wang JR,Sridharan V,et al. Pharmacological induction of transforming growth factor-beta1 in rat models enhances radiation injury in the intestine and the heart[J].PLoS One,2013,8(7):e70479.DOI:10.1371/journal.pone.0070479. [23] Boerma M,Roberto KA,Hauer-Jensen M.Prevention and treatment of functional and structural radiation injury in the rat heart by pentoxifylline and alpha-tocopherol[J].Int J Radiat Oncol Biol Phys,2008,72(1):170-177.DOI:10.1016/j.ijrobp.2008.04.042.