心脏磁共振成像T1 mapping技术检测2型糖尿病小鼠早期心肌纤维化的实验研究  

The research of detecting early myocardial fibrosis by cardiac magnetic resonance T1mapping in type 2 diabetic cardiomyopathy mouse model

作　　者：张宏凯 石春彦 张楠[1] 李国旗 杨琳[1] 刘东婷[1] 李宇[1] 范占明[1] ZHANG Hongkai;SHI Chunyan;ZHANG Nan;LI Guoqi;YANG Lin;LIU Dongting;LI Yu;FAN Zhanming(Department of Radiology,Beijing Anzhen Hospital,Capital Medical University,Beijing Institute of Heart,Lung and Blood Vessel Diseases,Beijing 100029,China)

机构地区：[1]首都医科大学附属北京安贞医院-北京市心肺血管疾病研究所医学影像科,100029

出　　处：《心肺血管病杂志》2020年第7期860-867,共8页Journal of Cardiovascular and Pulmonary Diseases

基　　金：国家自然科学基金常规面上项目(81771791);北京市医院管理中心“青苗”计划专项经费(QML20190607)。

摘　　要：目的:应用心脏磁共振成像(CMRI)T1 mapping技术,分析2型糖尿病(T2DM)模型早期弥漫性心肌纤维化的影像学特征,探索糖尿病心肌病(DCM)早期诊断及疾病进展动态评价的无创影像学指标。方法:选取30只健康,4周龄,C57BL/6 J雄性小鼠,随机分为对照组(对照组,n=10)和实验组(T2DM,n=20)。对照组普通饲料喂养;实验组,高脂饮食喂养4周后,单次大剂量腹腔注射链脲佐菌素(streptozotocin,STZ)制作T2DM模型,对照组注射等剂量柠檬酸盐缓冲液,并于造模成功后第4周(4 W)、第8周(8 W)、第12周(12 W)、第16周(16 W),应用7.0T磁共振设备,采集心脏电影(cine)、延迟强化(LGE)图像,同时运用Look-Locker序列采集Pre-T1mapping和post-T1mapping图像,并测量血细胞压积(HCT),计算细胞外容积分数(ECV)。同期,取心肌进行天狼星红染色,观察心肌组织病理改变并计算胶原容积分数(CVF)。多组间计量资料均数比较采用单因素方差分析(ANVOA);两组间计量资料均数比较采取独立样本t检验;两变量间相关性分析采用皮尔森线性相关分析。结果:每个时间节点对照组和T2DM组各有6只小鼠纳入统计学分析。实验过程T2DM组小鼠血糖均>13.89 mmol/L;同时随着糖尿病病程的进展,T2DM组ECV值和CVF值逐渐升高,并于第12周时较对照组差异有统计学意义[(31.1±1.2)%vs.(28.1±1.8)%,P=0.044;CVF(6.4±0.8)%vs.(3.3±1.1)%,P=0.004],早于心功能改变;同时,ECV和CVF高度相关(r=0.849,P<0.001)。结论:CMRI T1mapping技术能够在DCM早期准确检测弥漫性心肌纤维化,ECV值的动态变化可作为评价疾病进展的有效影像学指标。Objective:The T2DM mice were scanned continuously by cardic magnetic resonance imaging(CMR)with collagen volume fraction(CVF)at multiple time points,and dynamically monitored the changes of early diffuse myocardial fibrosis.Importantly,to establish the early quantitative imaging detection standard was needed in T2DCM.Methods:Thirty C57BL/6 J(4 weeks old)male mice were randomly divided into two groups:control group(n=10),T2DM group(n=20).The mice received a sustained normal diet in control group;the mice received a sustained high-fat diet(HFD)and were received intraperitoneal injection of streptozotocin(STZ)in T2DM group after 4 weeks.The 7.0T MRI was applied at 4,8,12 and 16 weeks after post-successful model,including cardiac cine,late gadolinium enhancement(LGE)and T1mapping imaging.Extracellular volume fraction(ECV)was calculated by hematocrit(HCT),Pre and Post-T1 value.Meanwhile,sirian red staining was performed to observe the changes of myocardial tissue and calculate CVF.The differences between any two of the multiple groups were analyzed by ANOVA.ECV and CVF values were compared using Pearson’s correlation coefficients.Results:Six mice in the control group and T2DM group were included in the statistical analysis at multiple time points.With the progression of the diabetes,the ECV and CVF values gradually increased;there was significant statistical difference at 12 weeks after post-successful model[ECV T2DM(31.1±1.2)%vs.control(28.1±1.8)%,P=0.044;CVF T2DM(6.4±0.8)%vs.control(3.3±1.1)%,P=0.004].The ECV value was a strong correlation with CVF(r=0.849,P<0.001).Conclusions:CMR T1mapping can be used to dynamically detect early myocardial fibrosis in T2DM mice,early diagnosis of DCM and the evaluation of progression disease.

关 键 词：糖尿病心肌病 心脏磁共振成像 T1 mapping技术 细胞外容积分数 小鼠 

分 类 号：R54[医药卫生—心血管疾病]