不同造模时间对小鼠射血分数保留型心力衰竭模型的影响

Effect of Different Time of Modeling on Mice with Heart Failure with Preserved Ejection Fraction

目的诱导C57BL/6N小鼠建立射血分数保留型心力衰竭(heart failure with preserved ejection fraction,HFpEF)模型,探索最佳成模时间。方法24只5周龄雄性C57BL/6N小鼠以高脂饲料及含一氧化氮合酶抑制剂L-NAME水喂养,分别于喂养4、8、12周随机选取8只进行体重、血压、运动功能、超声功能分析后处死。另取8只5周龄雄性C57BL/6N小鼠作为对照组常规饲料及水喂养。各组小鼠取材后测量肺湿/干重比及心脏重量/胫骨长度比。结果与对照组相比,造模4、8、12周的小鼠体重、血压、反映舒张功能障碍的超声指标E/E’及E/A,左室舒张末期容积,左室舒张期内径均升高,运动耐力均下降;取材后与对照组相比,三组肺湿干比及心脏胫骨长比均升高。上述指标以第8周及第12周的小鼠差异更为显著,其中第12周各指标标准差更小,说明造模12周的小鼠HFpEF的模型更加稳定。结论HFpEF小鼠模型造模第12周具更好稳定性及成模率更高。

Objective To explore the optimal modeling time of heart failure with preserved ejection fraction(HFpEF)induced in C57BL/6N mice.Methods Twenty-four 5-week-old male C57BL/6N mice maintained on high-fat chow and water containing 0.5 g/L nitric oxide synthase inhibitor N(gamma)-nitro-L-arginine methyl ester(L-NAME)were executed after 4,8 and 12 weeks respectively.Eight male C57BL/6N mice at 5 weeks of age were taken as the control group fed with normal chow and water and executed after 12 weeks.HFpEF mice were evaluated for body weight,blood pressure,exercise function and ultrasound function before execution,while control mice were evaluated for the above functions at 4,8 and 12 weeks.The lung wet/dry weight ratio and heart weight/tibial length ratio were measured and calculated after mice sampling.Results Compared with control mice at the corresponding time points,body weight,blood pressure,the ratio of early mitral filling velocity/early diastolic mitral annular velocity(E/E’ratio),the ratio of early mitral filling velocity/late mitral filling velocity(E/A ratio),left ventricular end-diastolic volume,and left ventricular end-diastolic diameter were all increased and exercise tolerance was decreased;after sampling,the ratios of lung wet/dry weight and heart weight/tibial length were increased in all three groups compared to control.The differences in these indicators were more significant at week 8 and 12 of modeling,and the variance of these indicators was smaller after 12weeks.Conclusions The difference in the HFpEF mouse model was more pronounced at 8 and 12 weeks of modeling,with better stability and higher modeling rates particularly for 12-week.