基于7.0 T心脏MR评估2型糖尿病小鼠早期心肌应变改变特点

Early myocardial strain characteristics in type 2 diabetic mellitus mice evaluated by 7.0 T cardiac MR

目的旨在探讨糖尿病心肌病(DCM)早期心肌应变的改变特点。方法60只健康4周龄雄性C57BL/6J小鼠,采用随机数字法分为2型糖尿病(T2DM)组(30只)和对照组(30只)。对照组采用普通饲料喂养,T2DM组采用高脂饲料喂养。喂养4周后,T2DM组单次大剂量腹腔注射链脲佐菌素(STZ)溶液制作T2DM模型,最终造模成功23只。对照组注射等剂量柠檬酸钠缓冲液。造模成功后第4、8、12、16、20和24周作为监测时间点采集实验数据。每个时间点时各组均入组9只小鼠,然后各组随机选取6只用于体重和血糖监测及7.0 T MR图像采集,处死剩余3只用于制作病理切片(天狼星红染色)以观察心肌间质纤维成分及微小血管的情况。MR图像采用心脏MR特征追踪(CMR-FT)技术进行分析,获得左心室整体周向应变峰值(GPCS)和径向应变峰值(GPRS),并测量射血分数(EF)等。观察期内,各组自身不同监测点参数间比较采用单因素方差分析;组间参数比较采取两独立样本t检验。结果观察期内组间血糖值差异均有统计学意义(P<0.05)。观察期(4~24周)内T2DM组小鼠GPCS呈下降趋势,组内差异有统计学意义(F=8.23,P<0.001);与对照组相比,T2DM组小鼠的GPCS于第20、24周时组间差异具有统计学意义。第20周时T2DM组GPCS为-11.4%±2.1%,对照组为-14.3%±1.9%(t=-2.54,P=0.029);第24周时T2DM组为-12.3%±1.7%,对照组为-14.6%±1.8%(t=-2.35,P=0.040)。EF在第24周时组间差异有统计学意义,T2DM组为51%±5%,对照组为62%±6%(t=3.38,P=0.007)。观察期内,T2DM组小鼠GPRS呈下降趋势,但组内和组间均差异无统计学意义(P>0.05)。心肌组织病理切片显示从第12周起T2DM组小鼠心肌间质纤维成分明显增多。结论T2DM小鼠早期即可出现心肌间质纤维化和心肌应变的改变,其中左心室整体周向应变峰值可较EF更早反映DCM的心功能改变。

Objective To investigate the characteristics of early myocardial mechanics changes in diabetic cardiomyopathy(DCM).Method Sixty healthy 4-week-old male C57BL/6J mice were randomly divided into the T2DM group(n=30)and the control group(n=30).The T2DM group was fed with high-fat diet for 4 weeks,and accepted injection of a single high-dose of streptozotocin(STZ)intraperitoneally.Finally,the model was established successfully in 23 mice.The control group was fed with a normal diet and treated with citrate buffer liquid at an equal dose as T2DM group.Then,nine mice were randomly selected from each of the two groups every 4 weeks until the end of the 24th week.Six of the nine mice were randomly selected to perform 7.0 T MR scanning after measuring blood glucose and body weight.Cine images were acquired through cardiovascular MR feature tracking(CMR-FT).The obtained parameters included the left ventricle global peak circumferential strain(LV-GPCS),left ventricle global peak radial strain(GPRS)and the ejection fraction(EF),etc.The rest three mice were sacrificed for observation of the changes of interstitial fibers and micro-vessels in myocardial tissue with Sirius red staining.One-way analysis of variance(ANOVA)and t test were used for comparison.Results There were significant differences in blood glucose levels between the two groups during the observation period(P<0.05).In the 4^(th)-24^(th) week,the value of GPCS in T2DM group showed a downward trend,and the difference was statistically significant(F=8.23,P<0.001).Compared with the control group,the value of GPCS in T2DM group was statistically significant at the 20^(th) and 24^(th) week(the 20^(th) week:-11.4%±2.1% in the T2DM group vs.-14.3%±1.9% in the control group,t=2.54,P=0.029;the 24^(th) week:-12.3%±1.7% in the T2DM group vs.-14.6%±1.8% in the control group,t=2.35,P=0.040),while the EF value was different at the 24^(th) week(51%±5% in the T2DM group vs.62%±6% in the control group,t=3.38,P=0.007).There was no significant difference in the GPRS of the T2DM mice group over time or compared with the controls(P>0.05).Moreover,the pathological results showed that the myocardial interstitial fibers in the T2DM group had remarkably increased since the 12^(th) week.Conclusions The alterations in myocardial interstitial fibers and myocardial contractility appeared early in T2DM mice.Especially,the left ventricle global peak circumferential strain value is superior to the EF value in reflecting the early changes in DCM.