Mechanism of radiation combined with recombinant human endostatin in inducing myocardial fibrosis

中华放射肿瘤学杂志 Pub Date : 2020-04-15 DOI:10.3760/CMA.J.CN113030-20190911-00009

Yanfang Wan, W. Ouyang, S. Su, Jun Zhang, Shi-Lin Xu, Zhu Ma, Qingsong Li, Y. Geng, B. Lu

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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. Key words: Radiation-induced heart disease; Recombinant human endostatin; TGF-β1 gene; Smad2 gene; Smad3 gene; Collagen-I gene

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放射联合重组人内皮抑素诱导心肌纤维化的机制

目的建立实验动物模型，揭示放射性心肌纤维化的机制，验证重组人内皮抑素通过TGF-β1、Smad2和Smad3信号通路在加重放射性心肌纤维化过程中的作用。方法60只雄性成年Sprague-Dawley大鼠随机分为放疗组（RT）2 5Gy、重组人内皮抑素（RE）6 mg/kg、RE 12 mg/kg、RT 2 5Gy+RE 6 mg/kg、RT 25 Gy+RE 12 mg/kg和空白对照组。干预后1个月和3个月，每组处死5只大鼠。采集心肌组织。苏木精-伊红染色观察病理变化。通过Masson三色染色评估纤维化程度。用实时PCR和Western印迹法定量测定TGF-β1、Smad2、Smad3和Collagen-I mRNA和蛋白的表达水平。结果干预后3个月，Masson三色染色显示，RT25Gy和RT25Gy+RE（6和12mg/kg）组的胶原沉积比对照组更显著。此外，与对照组相比，这些组的TGF-β1、Smad2、Smad3和Collagen-I mRNA和蛋白的表达水平显著上调。结论总物理剂量为25Gy的辐射可诱导SD大鼠心肌纤维化。TGF-β1和Smad2信号通路是辐射联合重组人内皮抑素诱导心肌纤维化的常见信号通路。关键词：放射性心脏病；重组人内皮抑素；TGF-β1基因；Smad2基因；Smad3基因；胶原-I基因

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来源期刊

中华放射肿瘤学杂志

自引率

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发文量

6375

期刊介绍： The Chinese Journal of Radiation Oncology is a national academic journal sponsored by the Chinese Medical Association. It was founded in 1992 and the title was written by Chen Minzhang, the former Minister of Health. Its predecessor was the Chinese Journal of Radiation Oncology, which was founded in 1987. The journal is an authoritative journal in the field of radiation oncology in my country. It focuses on clinical tumor radiotherapy, tumor radiation physics, tumor radiation biology, and thermal therapy. Its main readers are middle and senior clinical doctors and scientific researchers. It is now a monthly journal with a large 16-page format and 80 pages of text. For many years, it has adhered to the principle of combining theory with practice and combining improvement with popularization. It now has columns such as monographs, head and neck tumors (monographs), chest tumors (monographs), abdominal tumors (monographs), physics, technology, biology (monographs), reviews, and investigations and research.