射血分数保留的心力衰竭模型建立及心脏结构特征的超声学评价

Establishment of a model of heart failure with preserved ejection fraction and ultrasonic evaluation of cardiac structural characteristics

目的评价高血压大鼠(SHR)结合高脂饲料和糖尿病因素建立射血分数保留的心力衰竭(HFpEF)模型的心脏结构和病理特征。方法将SPF级、14周龄的SHR大鼠随机分为SHR组(正常饲料喂食)10只、HFpEF组[高脂高糖饲料喂食结合腹腔注射链脲佐菌素(STZ,25 mg/kg体重)造成糖尿病复合模型]10只,另设SPF级、14周龄相同遗传背景的WKY大鼠10只作为空白对照组(WKY组),饲养持续8周。多普勒超声检测心脏功能指标:同一心动周期的舒张早期二尖瓣血流速度(E)、二尖瓣心房收缩期最大血流速度(A)、室间隔侧舒张早期二尖瓣环心肌运动速度(e′)、左房射血分数(LAEF)和左室射血分数(LVEF);心脏形态学的左心房内径参数、右心房内径参数和室间隔厚度(IVST)。血清学常规检测葡萄糖(GLU)和糖化血清蛋白(GSP)。酶联免疫吸附测定法(ELSIA)检测胰岛素(INS)、胰高血糖素(PG)、C肽(C-P)、瘦素(LEP)、心钠素(ANP)和B型脑尿钠肽(BNP)。大鼠心脏组织行HE染色,光学镜下观察心房/心室组织形态变化。结果SHR大鼠喂食高脂结合糖尿病造模形成HFpEF的病理特征,超声学检测表明,与WKY组比较,HFpEF组的E、E/A及E/e′显著增加(均P<0.01),e′及LAEF显著降低(均P<0.01);HFpEF组大鼠左心房前后径和左右径、右心房上下径不同程度增大(均P<0.05),IVST也显著增厚(P<0.01);同时大鼠心肌组织可见心房壁明显增厚,心肌细胞排列紊乱,可见纤维断裂。与WKY组比较,HFpEF血清标记物ANP和BNP含量显著升高(均P<0.01),血清胰岛素相关指标INS、PG、C-P、LEP、GSP及GLU含量不同程度升高(均P<0.01)。结论SHR大鼠结合高脂饲料和糖尿病因素建立的复合模型能够模拟HFpEF的多普勒超声学改变及病理特征,血清相关标记物和胰岛素指标异常变化。

Objective To evaluate the pathological features of a heart failure with preserved ejection fraction(HFpEF)model,which is established by spontaneously hypertensive rats(SHR)through high-fat diet and diabetic factors.Methods Twenty specific pathogen-free grade(SPF grade)and 14-week-old SHR rats were randomly divided into SHR group(normal diet)and HFpEF group[high-fat diet combined with intraperitoneal injection of streptozotocin(STZ,25 mg/kg)were used to create a diabetic complex model]with 10 rats in each group.Ten SPF and 14-week-old WKY rats with the same genetic background were set as blank control group(WKY group).All rats were fed for 8 weeks.Echocardiography was performed to measure cardiac parameters:peak velocity of early diastolic mitral inflow(E),peak velocity of late diastolic mitral inflow(A),and the early diastolic mitral annulus e′in the same cardiac cycle,left atrial ejection fraction(LAEF),left ventricular ejection fraction(LVEF),left atrial diameter,right atrial diameter and interventricular septal thickness(IVST).Serological testing included glucose(GLU)and glycosylated serum protein(GSP);Enzyme-linked immunoassay(ELISA)testing included insulin(INS),glucagon(PG),C-peptide(CP),leptin(LEP),atrial natriuretic peptide(ANP)and B-type brain natriuretic peptide(BNP).The rat heart tissue was stained with HE,and the morphological changes of atrial/ventricular tissue were observed under an optical microscope.Results The pathological characteristics of HFpEF was established in SHR rats fed with high fat and diabetes.Echocardiography showed that compared with the WKY group,the values of E,E/A and E/e′in the HFpEF group were significantly increased(all P<0.01),and e′and LAEF were significantly reduced(all P<0.01).In the HFpEF group,the anteroposterior and tranverse dimensions of the left atrium and the long-axis dimension of the right atrium increased to varying degrees(all P<0.05),and the IVST was also significantly increased(P<0.01).At the same time,atrial wall was thickened obviously,myocardial cells were disordered,and myocardial fibers were broken.Compared with the WKY group,the levels of serum markers ANP and BNP in HFpEF group were significantly increased(all P<0.01),and the levels of serum insulin-related indicators INS,PG,CP,LEP,GSP,and GLU increased to varying degrees(all P<0.01).Conclusions The composite model established by SHR rats through high-fat diet and diabetic factors can simulate the Doppler echocardiographic changes and pathological features of HFpEF,as well as abnormal changes in serum related markers and insulin indicators.