内质网应激凋亡蛋白在恩度与照射致大鼠心脏损伤中的作用  

Role of endoplasmic reticulum stress apoptosis protein in cardiac injury induced by endostar plus irradiation in rats

作　　者：陈琪颖 曹东东 欧阳伟炜 黄丽 苏胜发 马筑 李青松 耿一超 杨文刚 陈霞霞 刘杰 卢冰 Chen Qiying;Cao Dongdong;Ouyang Weiwei;Huang Li;Su Shengfa;Ma Zhu;Li Qingsong;Geng Yichao;Yang Wengang;Chen Xiaxia;Liu Jie;Lu Bing(Department of Oncology,the Affiliated Hospital of Guizhou Medical University,Guiyang 550004,China;Department of Oncology,the Affiliated Cancer Hospital of Guizhou Medical University,Guiyang 550004,China;Department of Oncology,Clinical Medical College,Guizhou Medical University,Guiyang 550004,China)

机构地区：[1]贵州医科大学附属医院肿瘤科,贵阳550004 [2]贵州医科大学附属肿瘤医院肿瘤科,贵阳550004 [3]贵州医科大学临床医学院肿瘤学教研室,贵阳550004

出　　处：《中华放射肿瘤学杂志》2023年第10期920-927,共8页Chinese Journal of Radiation Oncology

基　　金：国家自然科学基金(81660507);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);贵州省教育厅创新课题组研究项目([2016]032)。

摘　　要：目的:研究恩度联合低剂量X线照射后,内质网应激(ERS)及凋亡蛋白与大鼠心肌病理改变的关系。方法:40只SD大鼠平均分为对照组(腹腔注射等体积生理盐水,1次/d,14 d)、恩度组(腹腔注射恩度6 mg/kg,1次/d,14 d)、照射组(15 Gy分3次X线照射)、联合组(照射后腹腔注射恩度,剂量、时间同恩度组)。处理后1、6个月,取大鼠心肌组织,行HE染色、Masson染色观察心肌组织学改变,TUNEL法检测心肌细胞凋亡,ImageJ软件计算心肌胶原容积分数(CVF)。蛋白质印迹法检测ERS及凋亡蛋白葡萄糖调节蛋白78(GRP78)、类蛋白激酶内质网激酶(PERK)、C/EBP同源蛋白(CHOP)、胱天蛋白酶12(Caspase-12)表达水平。使用GraphPad Prism 8.0.1软件行单因素方差分析,组间两两比较采用t检验。结果:处理后6个月,照射组和联合组的心肌组织间质增宽,呈条索状或网状纤维化改变,心肌间质弥漫性胶原纤维沉积,与对照组比较,CVF显著增加(P均<0.01)。处理后1、6个月,联合组心肌细胞凋亡指数明显高于对照组(P<0.05、<0.001)。处理后1、6个月,照射组、联合组的GRP78蛋白表达量较对照组增加(P均<0.05),联合组的PERK、CHOP蛋白表达量较对照组增加(P均<0.01)。处理后6个月,照射组PERK、CHOP蛋白表达量较对照组增加(P均<0.05)。与对照组相比,恩度组、照射组、联合组在处理后1、6个月Caspase-12蛋白表达量均增加(P均<0.05)。结论:ERS及凋亡蛋白表达与大鼠放射性心脏损伤有关,低剂量X线照射联合恩度处理后ERS加重,心肌细胞凋亡增加。Objective To study the relationship between endoplasmic reticulum stress(ERS)and apoptotic protein and myocardial pathological changes in rats after endostar combined with low-dose X-ray irradiation.Methods Forty SD rats were evenly divided into four groups:control group(intraperitoneal injection of equal volume physiological saline,once per day,14 d),endostar group(intraperitoneal injection of endostar 6 mg/kg,once per day,14 d),irradiation group(15 Gy divided into 3 times X-ray irradiation)and combination group(intraperitoneal injection of endostar after irradiation at the same dose and time as the endostar group).At 1 and 6 months after treatment,myocardial tissues of rats were prepared for HE staining and Masson staining to observe the myocardial histological changes.TUNEL assay was used to detect myocardial cell apoptosis,and Image)software was utilized to calculate myocardial collagen volume fraction(CVF).The expression levels of ERS and apoptotic protein glucose-regulated protein 78(GRP78),protein kinase-like endoplasmic reticulum kinases(PERK),CCAAT/enhancer binding protein homologous protein(CHOP)and cysteine-containing aspartate-specific protease-12(Caspase-12)were detected by Western blot.One-way ANOVA was conducted using GraphPad Prism 8.0.1 software,and comparison between two groups was conducted using t-test.Results At 6 months after treatment,the myocardial interstitium in the irradiation and combination groups was widened,showing strip-like or reticular fibrosis changes,and the myocardial interstitium had diffuse collagen fiber deposition.Compared with the control group,CVF was increased significantly(both P<0.01).At 1 and 6 months after treatment,the apoptotic index of myocardial cells in the combination group was significantly higher than that in the control group(P<0.05,<0.001).At 1 and 6 months after treatment,the expression levels of GRP78 protein in the irradiation and combination groups were increased(all P<0.01),and the expression levels of PERK and CHOP proteins in the combination group w

关 键 词：内质网应激 恩度 X线照射 放射性心脏损伤 细胞凋亡 

分 类 号：R818[医药卫生—放射医学]