9.4T心脏磁共振特征追踪成像评估敲除Bach1基因对多柔比星诱导心脏毒性的保护  

Evaluation of the protection of Bach1 gene knockout against doxorubicin-induced cardiotoxicity based on 9.4T cardiovascular magnetic resonance feature-tracking

作　　者：王焱炜 杨钰成 薛晨 张楠[4] 娄海燕 王翠艳 WANG Yanwei;YANG Yucheng;XUE Chen;ZHANG Nan;LOU Haiyan;WANG Cuiyan(Cheeloo College of Medicine,Shandong University,Jinan,Shandong 250012,China;Department of Radiology,Shandong Provincial Hospital,Jinan,Shandong 250021,China;Binzhou Medical University,Yantai,Shandong 264003,China;Research Center of Translational Medicine,Breast Center,Central Hospital affiliated to Shandong First Medical University,Jinan,Shandong 250013,China)

机构地区：[1]山东大学齐鲁医学院,山东济南250012 [2]山东省立医院放射科,山东济南250021 [3]滨州医学院医学影像学院,山东烟台264003 [4]山东第一医科大学附属济南市中心医院转化医学中心乳腺中心,山东济南250013

出　　处：《中华肿瘤防治杂志》2024年第21期1298-1305,共8页Chinese Journal of Cancer Prevention and Treatment

基　　金：山东省自然科学基金(ZR2019MH125)。

摘　　要：目的探讨9.4T心脏磁共振特征追踪(CMR-FT)成像评价多柔比星(DOX)诱导小鼠心脏毒性的价值。方法共纳入24只雄性C57BL/6小鼠,其中野生型(WT)鼠12只,Bach1基因敲除(Bach1^(-/-))鼠12只,随机数字表法分为WT组、Bach1^(-/-)组、WT+DOX组和Bach1^(-/-)+DOX组,每组6只。构建小鼠心脏毒性模型,后对小鼠行9.4T磁共振扫描,分析各组小鼠左心室常规心功能参数及心肌应变参数。检测小鼠血清中乳酸脱氢酶(LDH)含量。摘取心脏,计算心脏质量/体质量(HM/BM),并进行心肌损伤评分,计算心肌组织胶原容积分数(CVF)。采用单因素方差分析进行多组间差异性分析,Pearson相关分析评价左心室射血分数(LVEF)、LDH、CVF与左心室各整体心肌应变参数之间的相关性。结果与WT组比较,WT+DOX组小鼠左心室收缩末期内径[LVDs;(1.77±0.50)vs(2.82±0.36)mm]、LDH[(3067.41±284.77)vs(4626.12±448.57)U/L]和CVF[(2.74±0.66)%vs(13.15±2.67)%]升高,q值分别为6.284、12.630和13.610,P值分别为0.001、<0.001和<0.001;而LVEF[(79.98±3.68)%vs(55.16±3.25)%]、HM/BM[(5.54±0.18)%vs(4.59±0.07)%]、左心室整体径向应变[LVGRS;(47.45±4.33)%vs(27.52±2.95)%]、左心室整体周向应变[LVGCS;(-21.63±0.87)%vs(-16.38±1.79)%]和左心室整体纵向应变[LVGLS;(-20.58±1.59)%vs(-15.59±1.45)%]均降低,q值分别为18.820、16.990、10.620、9.841和8.325,均P<0.001。病理染色显示血管周围的心肌组织纤维化。与WT+DOX组相比,Bach1^(-/-)+DOX组小鼠的LVEF[(55.16±3.25)%vs(68.25±0.96)%]、LVGRS[(27.52±2.95)%vs(38.12±4.52)%]、LVGCS[(-16.38±1.79)%vs(-19.61±0.72)%]和LVGLS[(-15.59±1.45)%vs(-19.05±0.96)%]明显提高,q值分别为9.920、5.648、6.044和5.773,P值分别为<0.001、0.004、0.002和0.003,同时心肌损伤和心肌纤维化程度也得到明显改善。相关性研究中,LVEF与LVGRS之间相关性最强(r=0.883,P<0.001),LDH与LVGCS之间相关性最强(r=0.837,P<0.001),CVF与LVGRS间相关性最强(r=-0.749,P<0.001)。结论敲除Bach1First Medical University;Objective To investigate the value of 9.4T cardiac magnetic resonance feature-tracking(CMR-FT)imaging in evaluating doxorubicin(DOX)-induced cardiotoxicity in mice.Methods A total of 24 C57BL/6 male mice,including12 wild-type(WT)mice and 12 Bach1 knockout(Bach1^(-/-))mice,were divided by random number table method into the WT group,the Bach1^(-/-)group,the WT+DOX group and the Bach1^(-/-)+DOX group,with 6 mice in each group.A DOX-induced cardiotoxicity mouse model was constructed,then the mice were scanned with 9.4T magnetic resonance.The left ventricular routine cardiac function parameters and myocardial strain parameters were analyzed.Lactate dehydrogenase(LDH)levels in mous serum were measured.The hearts were extracted,and heart weight/body weight(HM/BM)was calculated.Myocardial injury score was assessed and collagen volume fraction(CVF)of myocardial tissues was calculated.One-way analysis of variance(ANOVA)was used for multi-group difference analysis.Pearson correlation analysis was used to evaluate the correlation between left ventricular ejection fraction(LVEF),LDH,CVF and left ventricular global myocardial strain parameters,Results Compared with the WT group,left ventricular end-systolic dimension[LVDs;(1.77±0.50)vs(2.82±0.36)mm],LDH[(3067.41±284.77)vs(462.6.12±448.57)U/L]and CVF[(2.74±0.66)%vs(13.15±2.67)%]were significantly increased in the WT+DOX group,with q values of 6.284,12.630,and 13.610,respectively,and P values of 0.001,<0.0.01,and<0.001,while LVEF[(79.97±3.68)%vs(55.16±3.25)%],HM/BM[(5.54±0.18)%vs(4.59±0.07)%],left ventricular global radial strain[LVGRS;(47.45±4.33)%vs(27.52±2.95)%],left ventricular global circumferential strain[LVGCS;(-21.63±0.87)%vs(-16.38±1.79)%]and left ventricular global longitudinal strain[LVGLS;(-20.58±1.59)%vs(-15.59±1.45)%]were decreased,with q values of 18.820,16.990,10.620,9.841,and 8.325,respectively,all P<0.001.Pathological staining showed perivascular myocardial fibrosis.Compared with the WT+DOX group,LVEF[(55.16±3.25)%vs(6

关 键 词：心脏毒性 心脏磁共振 特征追踪 应变 Bach1 

分 类 号：R73-36[医药卫生—肿瘤] R445.2[医药卫生—临床医学]