%0 Journal Article
%T 曲美他嗪对放射性心脏损伤的保护作用及其机制
%A 张金梦　白馨雅　孙洋　何信佳　王林芳　安永恒
%J -
%D 2020
%R 10.13362/j.jpmed.202002009
%X 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。<br>Abstract：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
%K 放射疗法
%K 辐射损伤
%K 心脏损伤
%K 结缔组织生长因子
%K 转化生长因子β1
%K 曲美他嗪
%K 小鼠
%K 近交C57BL<br>Radiotherapy
%K Radiation injuries
%K Heart injuries
%K Connective tissue growth factor
%K Transforming growth factor beta1
%K Trimetazidine
%K Mice
%K inbred C57BL
%U http://jpmed.qdu.edu.cn/CN/10.13362/j.jpmed.202002009