大鼠冠脉微栓塞后心功能动态变化的实验研究

Dynamic alteration of left ventricular function in a rat model with coronary microembolization

目的：动态观察大鼠冠脉微栓塞（CME）后亚急性期及慢性过程中的心功能变化规律与特征，并探讨其变化的病理基础。方法：以SD大鼠为研究对象，用自身血凝块制成的血栓微粒造成心肌内小冠脉栓塞，建立CME模型。16只大鼠被随机分成两组：对照组8只、模型组8只。应用VIVID-7超声显像仪分别同步记录模型构建前、构建后1周、4周大鼠CME模型组和对照组二维超声心动图（2DE）、解剖M型超声心动图（AME）图像或曲线并进行观察指标的测量分析；观察指标为左室壁各节段（各壁）收缩期与舒张期厚度（WTs、WTd）及各节段室壁增厚率（WTF），左室收缩与舒张末期内径（LVEDS、LVEDD）和射血分数（LVEF）。模型构建后4周处死动物取心肌标本，应用显微图像处理系统结合HE染色定量观察心肌组织内微小梗死灶数（Nmmi）、结合天狼星红染色定量检测心肌组织胶原纤维的含量（Fcf）。结果：对照组各超声测量指标在各阶段均无显著变化，CME模型组各指标在各阶段发生不同程度显著变化：左室各节段WTF及LVEF在术后1周和4周较术前显著降低（P〈0．05～〈0.01），且术后4周减低较术后1周更显著（P〈0．05～〈0．01）。模型组LVEF、前间隔和后壁wTF分别均与Nmmi和Fcf呈高度相关性（r均〉0．70，P〈0．05～〈0．01）。结论：大鼠冠脉微栓塞后亚急性及慢性过程中发生了进行性心肌收缩功能减退，其病理基础是弥漫性微小心肌梗死及间质纤维化。

Objective： To observe the dynamic changes of ventricular systolic function in a rat model with coronary micro embolization （CME） in subacute and chronic phases, and to explore the mechanisms of the changes. Methods： A rat model of CME was created by injecting a suspension of microthrombotic particles into left ventricle when clamping the ascending aorta. The microthrombotic particles were generated from the rat clots. Sixteen rats were randomly divided into two groups： Control group （n=8） and model group （n= 8）. Echocardiography by using anatomical M-Mode （AME） was performed at baseline, and 1 week and 4 week after CME. The parametric measurements include systolic and diastolic thickness of regional left ventricle （WTs and WTd） and systolic thickening fraction of regional left ventricle （WTF）, and left ventrieular ejection fraction （LVEF）. The animals were sacrificed at 4 weeks after CME. A microscopy incorporated with an image analysis software （ImagePro--4） was employed to calculate the number of micro-myocardial infarction （Nmmi） in sections with HE--staining, and to measure the fraction of collagen fiber （Fcf） in sections with Sirius--Red--staining. Results： All parameters derived echocardiography in control group were not changed at all stages. All parameters in model group significantly altered in various degrees at each stage, comparing with those measurements at baseline, WTF in each segment of the left ventricle and LVEF was significantly reduced 1 week, 4 week after CME （P〈0.05-〈0.01）, with more significant changes at 4 week （P〈0.05-〈0.01） ;LVEF and regional WTF were highly correlated with Nmmi and Fcf respectively （r〉0. 70, P〈0. 05-0.01）. Conclusion： Diffuse and progressive systolic function impairment generates during the process of CME from subacute phase to chronic phases, and its mechanism may be mainly due to interstitial myocardial fibrosis.