相同剂量分割照射与单次照射对小鼠放射性心脏损伤的影响  

Effects of the same dose of fractionated radiation and single radiation on the modeling of radiation⁃induced heart damage in mice

作　　者：曹虎 王唱垚 邵靖媛 刘杰[3] 王溢豪 何智超 胡舜英[3] 王华 CAO Hu;WANG Changyao;SHAO Jingyuan;LIU Jie;WANG Yihao;HE Zhichao;HU Shunying;WANG Hua(Academy of Military Medical Sciences,Academy of Military Sciences,Beijing 100850,China;College of Life Sciences,HebeiUniversity,Baoding,Hebei 071002,China;Department of Cardiology,Chinese PLA General Hospital,Beijing 100853,China;College of Life Sciences,Anhui Medical University,Hefei 230032,China)

机构地区：[1]军事科学院军事医学研究院,北京100850 [2]河北大学生命科学学院,河北保定071002 [3]解放军总医院心血管病医学部,北京100853 [4]安徽医科大学生命科学学院,合肥230032

出　　处：《军事医学》2024年第4期251-259,共9页Military Medical Sciences

基　　金：国家自然科学基金面上项目(82173450)。

摘　　要：目的探索相同剂量分割照射与单次照射对小鼠放射性心脏损伤的影响。方法野生型C57BL/6J小鼠21只,随机分为正常对照组、分割照射组和单次照射组。采用18 Gy X射线,对小鼠心脏分别进行分割(3 Gy/次,6次)和单次照射,建立放射性心脏损伤模型。照射后7和28 d通过全自动生化分析仪检测小鼠心肌酶损伤标志物肌酸激酶(CK)、肌酸激酶同工酶MB(CK-MB)、乳酸脱氢酶(LDH)和LDH1,以及外周血清离子(K^(+)、Ca^(2+)、Fe^(2+)和Cl^(-))的浓度;照射后28 d检测小鼠心脏功能,记录并分析左心室射血分数(EF)、左心室短轴缩短率(FS)、左心室舒张末期容积(LVEDV)、左心室质量(LV mass)和左心室收缩末期容积(LVESV)的变化;激光共聚焦显微镜观察心肌细胞线粒体膜通道孔(mPTP)开放和线粒体膜电位的改变;透射电镜观察心肌超微结构;Masson染色观察心肌纤维化;油红染色观察主动脉粥样硬化;实时定量PCR(RT-qPCR)和Western印迹检测凋亡相关基因与蛋白B细胞淋巴瘤-2相关蛋白X(BAX)和胱天蛋白酶3(casepase-3)的表达。结果18 Gy X射线照射后7 d,单次照射组小鼠CK、CK-MB、LDH和LDH1的表达水平均显著升高或有升高趋势,而分割照射组仅有CK和LDH1出现升高趋势。照射后28 d,2种照射方式均可导致心肌酶谱4种酶的表达水平升高。照射后7和28 d,2种照射方式均可导致血清离子K^(+)、Fe^(2+)、Ca^(2+)和Cl^(-)的浓度明显降低。2种照射方式都会导致EF和FS降低,LV mass、LVEDV和LVESV升高,2组之间EF和FS的差别具有统计学意义。分割照射和单次照射均会导致mPTP和膜电位的降低,其中单次照射组的改变更加显著,2组之间的差异具有统计学意义。电镜观察发现,X射线照射后心肌细胞线粒体嵴减少,空泡化形成以及心肌纤维束增粗。Masson染色可见,X射线照射后小鼠心肌组织胶原纤维沉积,单次照射组更明显。主动脉大体油红染色发现,2种照射方�Objective To explore the effects of the same dose of fractionated radiation and single radiation on radiationinduced heart damage in mice.Methods Twenty-one wild-type C57BL/6J mice were randomly divided into the normal group,fractionated radiation group and single radiation group.18 Gy X-ray,via fractionated(3 Gy/time,6 times)radiation or single radiation,was used to establish a radiation-induced heart damage model.The concentrations of myocardial enzyme damage markers(creatinekinase(CK),creatinekinase-MB(CK-MB),lactate dehydrogenase(LDH)and LDH1)and peripheral serum ions(K^(+),Ca^(2+),Fe^(2+)and Cl^(-))were detected by an automatic biochemical analyzer at day 7 and 28 after radiation.Ultrasound was used to detect and analyze the cardiac function of mice at day 28 after radiation,including the left ventricular ejection fraction(EF),left ventricular fractional shortening(FS),left ventricular end-diastolic volume(LVEDV),left ventricular mass(LV mass)and left ventricular end-systolic volume(LVESV).The opening of the mitochondrial permeability transition pore(mPTP)and changes of mitochondrial membrane potential of myocardial cells were observed using a laser confocal microscope.The ultrastructure of myocardia was observed under a transmission electron microscope(TEM)and cardiac fibrosis was checked by Masson staining.The atherosclerosis of the aorta was examined by gross oil red staining.Real-time quantitative PCR(RT-qPCR)and Western blotting were performed to detect the expressions of apoptosis-related genes and proteins,B cell lymphoma-2-associated X protein(BAX)and casepase-3.Results Seven days after 18Gy X-ray irradiation,the expression levels of CK,CK-MB,LDH and LDH1 in the single radiation group increased significantly or trended up,while only CK and LDH1 in the fractionated irradiation group continued to increase.Twenty-eight days after radiation,the expression levels of 4 enzymes in myocardial zymogram were increased by both radiation methods.Seven and twenty-eight days after radiation,the concentrations of s

关 键 词：放射性心脏损伤 小鼠 动物模型 分割照射 单次照射 

分 类 号：R818[医药卫生—放射医学] R541[医药卫生—临床医学]