Mechanism of radiation combined with recombinant human endostatin in inducing myocardial fibrosis
Wan Yan1, Ouyang Weiwei2, Su Shengfa2, Zhang Jun3, Xu Shilin1, Ma Zhu2, Li Qingsong2, Geng Yichao2, Lu Bing2
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 Pathology,Guizhou Medical University,Guiyang 550004,China
Abstract：Objective The experimental animal model was established to unravel the mechanism of radiation-induced myocardial fibrosis and validate the role of recombinant human endostatin in aggravating the process of radiation-induced myocardial fibrosis via the TGF-β 1, Smad2 and Smad3 signaling pathways. Methods Sixty male adult Sprague-Dawley rats were randomly divided into the following groups:radiotherapy (RT)25 Gy,recombinant human endostatin (RE) 6 mg/kg,RE 12 mg/kg,RT 25 Gy+RE 6 mg/kg,RT 25 Gy+RE 12 mg/kg and blank control groups. Five rats were sacrificed in each group at 1 and 3 months after interventions. The myocardial tissues were collected. The pathological changes were observed by Hematoxylin and eosin staining. The degree of fibrosis was assessed by Masson trichrome staining. The expression levels of TGF-β1,Smad2, Smad3 and Collagen-I mRNA and protein were quantitatively measured by real-time PCR and Western blotting. Results At 3 months after intervention, Masson trichrome staining revealed that the collagen deposition in the RT 25Gy and RT 25Gy+RE (6 and 12 mg/kg) groups was more significant than that in the control group. In addition, The expression levels of TGF-β1,Smad2, Smad3 and Collagen-I mRNA and protein in these groups were significantly up-regulated compared with those in the control group. Conclusions Radiation with a total physical dose of 25 Gy can induce myocardial fibrosis in the SD rat models. TGF-β 1 and Smad2 signaling pathways are the common signaling pathways of myocardial fibrosis induced by radiation combined with recombinant human endostatin.
Wan Yan,Ouyang Weiwei,Su Shengfa et al. Mechanism of radiation combined with recombinant human endostatin in inducing myocardial fibrosis[J]. Chinese Journal of Radiation Oncology, 2020, 29(4): 294-299.
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2020, Vol. 29 
