Mechanism of radiation combined with recombinant human endostatin in inducing myocardial fibrosis
10.3760/cma.j.cn113030-20190911-00009
- VernacularTitle: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
- Author:
Yan WAN
1
;
Weiwei OUYANG
;
Shengfa SU
;
Jun ZHANG
;
Shilin XU
;
Zhu MA
;
Qingsong LI
;
Yichao GENG
;
Bing LU
Author Information
1. 贵州医科大学肿瘤学教研室，贵阳 550004
- From:
Chinese Journal of Radiation Oncology
2020;29(4):294-299
- CountryChina
- Language:Chinese
-
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, Smad 2 and Smad 3 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-β 1, Smad 2, Smad 3 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-β 1, Smad 2, Smad 3 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 Smad 2 signaling pathways are the common signaling pathways of myocardial fibrosis induced by radiation combined with recombinant human endostatin.
