川崎病小鼠模型心脏超声评价

Assessment of echocardiography in a murine model of kawasaki disease

目的利用高频小动物心脏超声分析干酪乳杆菌细胞壁提取物(LCWE)诱导下川崎病(KD)疾病模型冠状动脉损伤的动态变化,为KD小鼠动物模型的制备及其功能评价提供依据。方法制备LCWE,取0.5 mL经腹腔单次注射制备C57BL/6小鼠的KD模型。将40只小鼠随机分为2组:KD模型组、正常对照组(磷酸盐缓冲液腹腔注射),每组20只。于LCWE注射后第10 d、21 d和60 d进行超声心动图检测,观察冠状动脉损伤动态变化。结果利用高频小动物超声心动仪成功测定了KD小鼠模型冠状动脉的变化,全部小鼠超声均检测到冠状动脉。KD模型组LCWE注射后10 d以及21 d,超声心动图显示冠状动脉管壁与血管周围出现高回声,左冠状动脉内径值比较,KD模型组左冠状动脉内径值(10 d:0.46±0.11 mm;21 d:0.47±0.09 mm)明显高于正常对照组小鼠(10 d:0.32±0.14 mm;21 d:0.36±0.06 mm),差异具有明显统计学意义(10 d:P=0.035;21 d:P=0.027),4(20%)只小鼠出现冠状动脉瘤样扩张改变;造模后60 d,KD模型组小鼠冠状动脉管壁弥漫性增厚,左冠状动脉主干内径较前缩小(0.43±0.11 mm),与正常对照组(0.38±0.02 mm)比较无明显差异(P>0.05),未见冠状动脉瘤样扩张改变。结论利用高频小动物心脏超声可获取小鼠清晰的冠状动脉图像,并能准确反映KD小鼠模型冠状动脉内径值动态变化;进一步证实LCWE诱导KD小鼠模型其冠状动脉损伤与自然病程状态的KD患儿冠状动脉损伤情况十分相似,可以很好的模拟KD冠状动脉损伤的形成过程;

Objective The aims of this study were to assess the developmental changes of coronary artery complications and Cardiac function in the murine model of kawasaki disease （KD） With a high frequency ultrasound system and to provide evidence for preparation the murine model of KD. Methods Lactobacillus casei cell wall extract （LCWE） was prepared, and injected to C57BL/6 mice intraperitoneally to induce KD. Totally 40 mice were categorized into 2 groups randomly： KD model group and the control group with intraperitoneal injection of phosphate buffered solution, 20 mice in each group. On days 10, 21 and 60, the coronary artery dimensions were measured by echocardiography. Cardiac function including left ventrieular end-diastolic diameter （LVIDd）, left ventricular end-systolic diameter（ LVIDs）, ejection fraction （EF）, fractional shortening（FS） and the blood flow velocity of atrioventricular valve during early diastole（E） /atrial contraction（A） were assessed. Results By echocardiography, the present study successfully detected coronary artery diameter and measured cardiac function in the murine model of KD. Two-dimensional echocardiography identified a high density echo images around the coronary artery wall at 10 days and 21 days following intraperitoneal injections of LCWE, and then, 4（20% ） accompanied by local coronary artery aneurysm at 14 days and 21 days. The left coronary artery showed dilation in the murine model group of KD at 10 days and 21 days following LCWE injection. The diameter of left coronary artery in the murine model of KD （0.46 ± 0. 11 mm on D10, 0.47 ± 0. 09 mm on D21 ）was significantly higher than the control group（0.32 ± 0. 14 mm on D 10, 0. 36 ± 0. 06 mm on D21, all P 〈 0.01 ）. The right coronary artery diameter had no significantly differences among each groups （ all P 〉 O. 05 ）. In addition, there were no significantly differences in measurement of cardiac function including EF,FS,E/A,LV Vol d,LV Vol s,LVID d and LVID s among each groups at lOdays, 21days and 60days following LCWE injection （all P 〉 0. 05）. Conclusions The present study successfully detected coronary arteries diameter and measured cardiac function by echocardiography in the murine model of KD. Our results suggested that the murine model of KD established by using an i.p. injection of L. casei cell wall extract was shown similar natural progression on coronary artery abnormalities with KD patient.