曲美他嗪对放射性心脏损伤的保护作用及其机制  

PROTECTIVE EFFECT OF TRIMETAZIDINE AGAINST RADIATION-INDUCED HEART DAMAGE AND ITS MECHANISM

作　　者：张金梦 白馨雅 孙洋[1] 何信佳[1] 王林芳[1] 安永恒[1] ZHANG Jinmeng;BAI Xinya;SUN Yang;HE Xinjia;WANG Linfang;AN Yongheng(Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao 266003, China)

机构地区：[1]青岛大学附属医院肿瘤科,山东青岛266003

出　　处：《精准医学杂志》2020年第2期129-133,共5页Journal of Precision Medicine

基　　金：青岛大学附属医院“临床医学+X”工程科研项目(2017-07-01)。

摘　　要：目的通过观察曲美他嗪对胸部照射后小鼠心肌损伤程度的影响,研究该药对小鼠放射性心脏损伤的保护作用及机制。方法雄性C57BL6小鼠60只随机分为6组:空白对照组(A组)小鼠不进行任何干预;模型组(B组)小鼠于实验第2周以6 MV-X线20 Gy单次照射小鼠胸部;照射+照射前低剂量给药组(C组)小鼠从第1天开始每天固定时间以10 mg/kg曲美他嗪灌胃,共9周,并于第2周开始与B组小鼠行相同照射;照射+照射前高剂量给药组(D组)小鼠从第1天开始每天固定时间以20 mg/kg曲美他嗪灌胃,共9周,并于第2周开始与B组行相同照射;照射+照射后低剂量给药组(E组)先于实验第2周开始与B组行相同照射,并于第3周开始每天固定时间以10 mg/kg曲美他嗪灌胃,共7周;照射+照射后高剂量给药组(F组)先于实验第2周开始与B组行相同照射,并于第3周开始每天固定时间以20 mg/kg曲美他嗪灌胃,共7周。实验结束后用苏木精-伊红(HE)染色观察小鼠心肌组织的形态学改变,采用免疫组织化学方法、实时荧光定量PCR方法检测小鼠心脏组织中结缔组织生长因子(CTGF)、转化生长因子-β1(TGF-β1)的表达。结果除A组外,其余各组小鼠心肌组织出现不同程度的病理改变,以炎性反应、纤维化为主。各组间CTGF、TGF-β1蛋白阳性表达率及其mRNA水平比较差异均有显著性(F=5.877~41.819,P<0.05);CTGF、TGF-β1蛋白阳性表达率及其mRNA水平,各给药组显著低于B组,C组高于D组,E组高于F组,A组显著低于其余各组(P<0.05);C组与E组、D组与F组比较差异无显著性(P>0.05)。结论曲美他嗪可减轻小鼠辐射诱导的心脏损伤,其发生机制可能与下调小鼠心脏组织中CTGF、TGF-β1表达有关。Objective To investigate the protective effect of trimetazidine against radiation-induced heart damage and its mechanism by observing the effect of trimetazidine on the degree of myocardial damage after chest irradiation in mice.Methods A total of 60 male C57BL6 mice were randomly divided into groups A,B,C,D,E,and F,with 10 mice in each group.The mice in group A(blank control group)were not given any intervention;the mice in group B(model group)were given single chest irradiation with 6 MV X-ray at 20 Gy at week 2 of the experiment;the mice in group C(irradiation and low-dose administration before irradiation)were given 10 mg/kg trimetazidine by gavage at a fixed time every day since day 1 for 9 weeks,followed by irradiation with the same regimen in group B;the mice in group D(irradiation and high-dose administration before irradiation)were given 20 mg/kg trimetazidine by gavage at a fixed time every day since day 1 for 9 weeks,followed by irradiation with the same regimen in group B;the mice in group E(irradiation followed by low-dose administration)were given irradiation with the same regimen in group B for the first two weeks of the experiment,followed by 10 mg/kg trimetazidine by gavage at a fixed time every day since week 3 for 7 weeks;the mice in group F(irradiation followed by high-dose administration)were given irradiation with the same regimen in group B for the first two weeks of the experiment,followed by 20 mg/kg trimetazidine by gavage at a fixed time every day since week 3 for 7 weeks.After the experiment ended,HE staining was used to observe the morphological changes of heart,and immunohistochemistry and quantitative real-time PCR were used to measure the expression of connective tissue growth factor(CTGF)and transforming growth factor-beta 1(TGF-β1)in heart tissue.Results All mice except those in group A had varying degrees of pathological changes of myocardial tissue,mainly inflammatory response and fibrosis.There were significant differences in the protein and mRNA expression rates of CTGF and

关 键 词：放射疗法 辐射损伤 心脏损伤 结缔组织生长因子 转化生长因子β1 曲美他嗪 小鼠 近交C57BL 

分 类 号：R818.74[医药卫生—放射医学] R654.2[医药卫生—临床医学]