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  

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

作　　者：万艳 欧阳伟炜 苏胜发 章俊 徐世林 马筑 李青松 耿一超 卢冰 Wan Yan;Ouyang Weiwei;Su Shengfa;Zhang Jun;Xu Shilin;Ma Zhu;Li Qingsong;Geng Yichao;Lu Bing(Teaching and Research Section of Oncology,Guizhou Medical University,Guiyang 550004,China;Department of Oncology,Guizhou Cancer Hospital,Affiliated Hospital of Guizhou Medical University,Guiyang 550004,China;Department of Pathology,Guizhou Medical University,Guiyang 550004,China)

机构地区：[1]贵州医科大学肿瘤学教研室,贵阳550004 [2]贵州医科大学附属医院/贵州省肿瘤医院肿瘤科,贵阳550004 [3]贵州医科大学病理学教研室,贵阳550004

出　　处：《中华放射肿瘤学杂志》2020年第4期294-299,共6页Chinese Journal of Radiation Oncology

基　　金：国家自然科学基金(NSFC81660507);中国国际医学交流基金会(Z-2014-06-19393);贵州省科技厅科技合作项目([2014]7135);贵州省应用基础研究计划重大项目([2015]2003);贵州省教育厅创新课题组研究项目([2016]032)。

摘　　要：目的建立实验动物模型探索放射性心肌纤维化的作用机制,验证重组人血管内皮抑制素可通过TGF-β1、Smad2、Smad3信号通路加重放射性心肌纤维化的过程.方法60只SD成年雄性大鼠随机分为25 Gy照射组、内皮抑制素6mg/kg组、内皮抑制素12 mg/kg组、25 Gy照射+内皮抑制素6mg/kg组、25Gy照射+内皮抑制素12 mg/kg组和对照组,分别在干预后1、3个月每组随机处死5只大鼠取心肌组织完成HE染色了解病理学改变,Masson染色了解纤维化程度,qPCR及Western Blot检测TGF-β1、Smad2、Smad3、Collagen-Ⅰ基因及蛋白表达.结果干预后3个月,25 Gy照射组、25 Gy照射+内皮抑制素(6、12mg/kg)组与对照组比较Masson染色见胶原沉积明显增加,TGF-β1、Smad2、Smad3、Collagen-Ⅰ蛋白及基因表达增加.结论给予大鼠总物理剂量为25Gy的照射,可诱导放射性心肌纤维化的发生.TGF-β1、Smad2信号通路是介导放射联合重组人血管内皮抑制素致心肌纤维化损伤的共同信号通路.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-β1,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-β1 and Smad2 signaling pathways are the common signaling pathways of myocardial fibrosis induced by radiation combined with recombinant human endostatin.

关 键 词：放射性心脏损伤 重组人血管内皮抑制素 TGF-Β1基因 SMAD2基因 SMAD3基因 Collagen-Ⅰ基因 

分 类 号：R730[医药卫生—肿瘤]