Zhang Xin-Xin, Du Zhong-Dong, Wen Shang-Guan, Sun Xiu-Ping
Department of Cardiology, Beijing Children's Hospital, Capital Medical University, Beijing 100045; Key Laboratory of Major Disease in Children, Ministry of Health, Beijing 100045, China.
Pediatric Cardiac Intensive Center, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China.
Chin Med J (Engl). 2017 Jun 20;130(12):1467-1474. doi: 10.4103/0366-6999.207461.
Murine model of coronary arterial inflammation has been widely accepted as an animal model of and used in Kawasaki disease (KD). This study sought to evaluate the developmental changes of coronary arteries and cardiac function in a murine model of KD with a high-frequency ultrasound system and to provide evidence for the preparation of the model of KD.
Lactobacillus casei cell wall extract was prepared and injected into C57BL/6 mice intraperitoneally (i.p.) to induce KD. A total of 120 mice were grouped into three groups. The intravenous immunoglobulin (IVIG) treatment group was i.p. injected with IVIG (2 g/kg), while the KD model and normal control groups were i.p. injected with 0.5 ml of phosphate buffered solution on day 5. All high-resolution echocardiography detection of mouse heart was performed by the same senior technician. Animal echocardiography was performed by measuring the coronary artery dimensions and cardiac function on days 0, 7, 14, 28, and 56 (high-resolution small animal ultrasound [Vevo770 pattern; VisualSonic, Canada] with broadband probe [RMVTM707B; frequency, 30 mHz; depth of focus, 1.2 cm]) which were measured and analyzed with Vevo770 software.
Pathological studies revealed focal inflammatory infiltrate asymmetrically distributed around the coronary artery trunk in the KD model group. Echocardiographic study including coronary dimension and cardiac function measurements was successfully performed in all subjects. The KD model and IVIG treatment groups showed left coronary artery dilation on days 7, 14, 28, and 56. The diameter of left coronary artery in the KD model group (0.53 ± 0.09 mm; 0.36 ± 0.07 mm; 0.34 ± 0.05 mm; 0.34 ± 0.04 mm) was significantly larger than those of IVIG treatment group (0.22 ± 0.02 mm; 0.28 ± 0.03 mm; 0.26 ± 0.03 mm; 0.27 ± 0.05 mm; 0.26 ± 0.03 mm; all P < 0.01) and the normal control group (0.21 ± 0.02 mm; 0.22 ± 0.03 mm; 0.22 ± 0.02 mm; 0.23 ± 0.02 mm; 0.27 ± 0.04 mm; all P< 0.01) on days 7, 14, 28, and 56. No significant differences were observed in the measurements of cardiac function among the groups on days 0, 7, 14, 28, and 56 (all P > 0.05).
Echocardiography could identify the consecutive changes of coronary artery in KD mice. Echocardiography is more convenient and direct in evaluating the coronary abnormalities in this animal model.
冠状动脉炎症小鼠模型已被广泛认可为川崎病(KD)的动物模型并应用于相关研究。本研究旨在利用高频超声系统评估KD小鼠模型中冠状动脉的发育变化及心脏功能,为KD模型的制备提供依据。
制备干酪乳杆菌细胞壁提取物并腹腔注射到C57BL/6小鼠体内以诱导KD。总共120只小鼠分为三组。静脉注射免疫球蛋白(IVIG)治疗组腹腔注射IVIG(2 g/kg),而KD模型组和正常对照组在第5天腹腔注射0.5 ml磷酸盐缓冲溶液。所有小鼠心脏的高分辨率超声心动图检测均由同一位资深技术人员完成。在第0、7、14、28和56天通过测量冠状动脉尺寸和心脏功能进行动物超声心动图检查(使用带有宽带探头[RMVTM707B;频率,30 mHz;聚焦深度,1.2 cm]的高分辨率小动物超声[Vevo770模式;VisualSonic,加拿大]),并用Vevo770软件进行测量和分析。
病理研究显示,KD模型组冠状动脉主干周围存在不对称分布的局灶性炎性浸润。所有受试者均成功进行了包括冠状动脉尺寸和心脏功能测量的超声心动图研究。KD模型组和IVIG治疗组在第7、14、28和56天出现左冠状动脉扩张。KD模型组在第7、14、28和56天的左冠状动脉直径(0.53±0.09 mm;0.36±0.07 mm;0.34±0.05 mm;0.34±0.04 mm)显著大于IVIG治疗组(0.22±0.02 mm;0.28±0.03 mm;0.26±0.03 mm;0.27±0.05 mm;0.26±0.03 mm;所有P<0.01)和正常对照组(0.21±0.02 mm;0.22±0.03 mm;0.22±0.02 mm;0.23±0.02 mm;0.27±0.04 mm;所有P<0.01)。在第0、7、14、28和56天,各组之间的心脏功能测量未观察到显著差异(所有P>0.05)。
超声心动图可识别KD小鼠冠状动脉的连续变化。在评估该动物模型中的冠状动脉异常方面,超声心动图更方便、直接。