应变技术定量评价肥胖小鼠左心室心肌收缩功能与早期炎症的关系

Quantitative Evaluation of the Relationship Between Left Ventricular Myocardial Systolic Function and Early Inflammation in Obese Mice by Strain Technique

目的验证应变技术对肥胖小鼠左心室收缩功能监测的有效性,通过与病理结合进一步说明肥胖所致心肌损伤改变与炎症因子的关系。材料与方法选取C57BL/6J雄性小鼠,经12周SPF级饲养建立肥胖动物模型,纳入肥胖组小鼠24只、对照组小鼠20只,采用Visualsonics Vevo 2100 Imaging System超声生物显微镜测量常规指标[室间隔舒张末期厚度(IVS-D)、室间隔收缩末期厚度(IVS-S)、左心室后壁舒张末期厚度(LVPW-D)、左心室后壁收缩末期厚度(LVPW-S)、左心室舒张末期内径(LVID-D)、左心室收缩末期内径(LVID-S)、左心室射血分数(LVEF)、左心室短轴缩短率(LVFS)]以及应用应变技术定量获取左心室心肌应变参数(纵向、径向和圆周应变参数)评价两组小鼠左心室收缩功能;通过病理大体形态、HE染色、天狼星红染色、小麦胚芽凝集素+异硫氰酸荧光素染色评价两组小鼠心肌组织改变。结果超声生物显微镜结果显示,与对照组相比,肥胖组小鼠LVEF[(75.04±2.81)%比(63.63±2.03)%]及LVFS[(43.17±2.63)%比(33.71±1.50)%]水平显著降低,LVID-S[(1.84±0.20)mm比(2.20±0.24)mm]、IVS-D[(0.78±0.09)mm比(1.01±0.06)mm]、IVS-S[(1.10±0.11)mm比(1.40±0.10)mm]、LVPW-D[(0.78±0.09)mm比(0.93±0.14)mm]及LVPW-S[(1.09±0.07)mm比(1.21±0.11)mm]显著增大(t=14.82、14.04、5.07、9.33、9.51、3.97、4.18,P均<0.001),纵向应变(24.81±2.97比9.43±2.49)、径向应变(26.56±5.46比19.17±8.03)及圆周应变值(26.49±5.40比14.25±6.03)均减低(t=11.91、2.40、4.65,P均<0.05)。病理结果显示,与对照组相比,肥胖组小鼠室间隔与左心室后壁明显增厚,心肌细胞肥大且排列紊乱,胶原纤维分布增多,NOD样受体热蛋白结构域相关蛋白-3炎症小体和半胱氨酸蛋白酶-1炎症因子明显呈高表达。结论超声生物显微镜可无创检测肥胖小鼠的心脏收缩功能,其应变技术可早期发现肥胖所致心肌损伤改变,NOD样受体热蛋白结构域相关蛋白-3炎症小体和半胱氨酸蛋白酶-1炎症因子参与肥胖小鼠心肌损伤过程。

Purpose To verify the effectiveness of strain technique in monitoring left ventricular systolic function in obese mice,and to further explain the relationship between myocardial injury caused by obesity and inflammatory factors by combining with pathology.Materials and Methods C57BL/6J male mice were selected,and the obese animal model was established after 12 weeks of SPF feeding,24 mice in the obesity group and 20 mice in the control group were included.Visualsonics Vevo 2100 Imaging System ultrasonic biomicroscopy(UBM)was used to measure the conventional indexes[interventricular septal end-diastolic thickness(IVS-D),interventricular septal end-systolic thickness(IVS-S),left ventricular posterior wall end-diastolic thickness(LVPW-D),left ventricular posterior wall end-systolic thickness(LVPW-S),left ventricular end-diastolic diameter(LVID-D),left ventricular end-systolic diameter(LVID-S),left ventricular ejection fraction(LVEF),left ventricular fractional shortening(LVFS)]and the strain parameters of left ventricle(longitudinal,radial and circumferential strain parameters)were obtained quantitatively by strain technique to evaluate the left ventricular systolic function of the two groups.The changes of myocardial tissue in the two groups were evaluated by pathological morphology,HE staining,Sirius red staining and wheat germ agglutinin+fluorescein isothiocyanate staining.Results The results of UBM showed that compared with the normal group,the levels of LVEF[(75.04±2.81)%vs.(63.63±2.03)%]and LVFS[(43.17±2.63)%vs.(33.71±1.50)%]in the obese group were significantly lower,while the levels of LVID-S[(1.84±0.20)mm vs.(2.20±0.24)mm],IVS-D[(0.78±0.09)mm vs.(1.01±0.06)mm],IVS-S[(1.10±0.11)mm vs.(1.40±0.10)mm],LVPW-D[(0.78±0.09)mm vs.(0.93±0.14)mm]and LVPW-S[(1.09±0.07)mm vs.(1.21±0.11)mm]were significantly increased(t=14.82,14.04,5.07,9.33,9.51,3.97,4.18,all P<0.001),and the values of long axial strain(24.81±2.97 vs.9.43±2.49),radial strain(26.56±5.46 vs.19.17±8.03)and circumferential strain(26.49±5.40 vs.14.25±6.03)decreased(t=11.91,2.40,4.65,all P<0.05).Pathological results showed that compared with the normal group,the interventricular septum and posterior wall of left ventricle were significantly thickened,cardiomyocytes were hypertrophic and disordered,collagen fibers were distributed more,NLRP3 inflammatory bodies and Caspase-1 inflammatory factors were significantly higher in obesity group.Conclusion UBM can noninvasively detect the cardiac systolic function of obese mice,and its strain technology can early detect the changes of obese myocardial injury.NLRP3 inflammatory body and Caspase-1 inflammatory factor are involved in the process of myocardial injury in obese mice.