【作者】 鲍晓峰；

【导师】 傅国胜；

【作者基本信息】 浙江大学 ， 内科学， 2004， 硕士

【摘要】 前言 冠状动脉粥样硬化性心脏病(CHD)是严重影响人类健康的心脏疾病，CHD的早期诊断、病变严重程度的评价和早期治疗有极其重要的作用。AMI作为CHD的急症之一，是人类心衰及死亡最常见的原因之一。动物实验在研究心肌梗死心功能方面有重要意义。由于大鼠与人类的基因高度同源，同时这种动物容易获取并且价格低廉，随着转基因技术的发展，可以作为良好的动物模型。研究者需要对大鼠心脏的形态、结构与功能有一种快速的检验和评价方法，无创性的心脏检查对这些小动物的活体评价有极其重要的作用。高频超声心动图、CT、MRI等方法可以对大鼠左室的形态、结构、功能等作出无创评价。但是CT、MRI价格高昂，操作复杂，并不是首选的评价方法。高频超声心动图能无创评价AMI大鼠的心脏的形态、结构、功能、血流情况。1990年De Simome、Pfeffer MA已开始应用多普勒超声心动图评价大鼠的心脏结构及功能。但是采用什么指标来评价大鼠心脏结构及功能的研究不多，不同时期与不同梗死面积的AMI大鼠心脏结构及功能的变化情况在文献上鲜有报道。DTI脉冲波技术(DTI-PW)在人类已证实是评价心肌运动及左室功能的良好技术，可以对心肌运动进行定量评价，但是能否评价大鼠节段心肌运动及功能，在文献中未见报道。我们通过不同时期正常与AMI大鼠的对照研究，旨在探讨①评价AMI大鼠的超声指标及不同时期AMI大鼠的左室重构情况。②DTI-PW能否评价大鼠节段心肌运动及功能。浙江大学硕士学位论文目的探讨高频超声心动图及DTI评价sP吨ue一Daw!ey大鼠(sD大鼠)心肌梗死模型心脏结构、功能及心肌运动的价值。方法一、大鼠心肌梗死模型制备 SD大鼠腹腔麻醉，气管插管，人工呼吸机辅助呼吸，左侧开胸，左冠状动脉前降支结扎致AMI。梗死面积)30%为大面积AMI组，梗死面积<30%为中小面积胡I组。二、实验方案(一)、AMI大鼠心脏结构及功能评价1、不同梗死面积AMI大鼠心脏结构与功能的比较 正常大鼠、AMI大鼠制备成功后饲养2周或8周，高频超声心动图检查;根据Masson二色染色分正常组、中小面积AMI组与大面积姗I组大鼠。比较不同梗死面积大鼠的心脏结构及功能。2、大面积AMI大鼠2周与8周时心脏结构与功能对照分析 胡I大鼠制备成功后饲养8周，2周时与8周时分别进行高频超声心动图检查心脏结构及功能;根据Masson三色染色确定大面积胡I大鼠。比较大面积AMI大鼠2周与8周时心脏结构及功能的改变。 (二)、正常大鼠与大面积AMI大鼠的心肌运动及二尖瓣口血流比较分析 正常大鼠、AMI大鼠制备成功后饲养8周，高频超声心动图检查，DTI检杏左室前壁与左室后壁的心肌运动速度，多普勒血流成像测定二尖瓣口血流速度;根据Masson二色染色确定大面积胡I组大鼠。比较正常大鼠与大面积AMI大鼠的心肌运动速度及二尖瓣口血流速度。(三)、超声测量可重复性及差异性分析。 正常人鼠饲养8周，同一检查者进行两次高频超声心动图与DTI检查，另外不同检杳者亦进行高频超声心动图与DTI检查，超声测量结果进行可重复性及差异性分析。三、心脏超声检查 大鼠腹腔内注射麻醉后，使用Acuson Sequoia 512超声诊断仪进行心脏超声检查，采用15L8w探头，探头频率为14姗z。左室短轴图像在乳头肌水平获得，以左室心外膜的弧状轮廓显示出来为理想:左室长轴图像通过垂直于短轴获得，以左室长度最长，包含二尖瓣和主动脉瓣为理想。舒张末期定义为左室容积最大时，收缩末期定义为左室容积最小时。测量浙江大学硕士学位论文左室长轴和左室短轴乳头肌水平M型曲线。测量左室内径、左室容量、左心功能、左心重量、左房内径、室间隔和左室后壁收缩期与舒张期厚度及收缩期增厚百分比等指标。在胸骨旁左室短轴乳头肌水平，用OTI一PW测定的左室前壁与左室后壁心肌运动频谱，记录土波Sm、Em、Am的峰值速度。在心尖四腔心切面用PW测定二尖瓣口血流频谱，记录舒张早期与舒张晚期的峰值速度。用MO储存资料供脱机分析。四、形态学分析五、统计学分析Masson二色染色，所有SD大鼠AMI模型的梗死面积经Masson二色染色确定。应用SPSS 11.0统计软件包进行统计分析处理。结果一、AMI大鼠心脏结构及功能评价、不同梗死面积AMI大鼠心脏结构与功能的比较1)、大鼠饲养2周组正常组、中小面积AMI组与大面积AMI组大鼠随着梗死面积的增人， 左室内径指标EDD、ESD增大，左室容量指标EDV、ESv增大，心功能指标EF、FS一卜降 (P<0.05，0.01)。 2)、大鼠饲养8周组正常组、中小面积阴I组与大面积胡I组大鼠随着梗死面积的增大， 左室内径指标EDD、ESD，左室容量指标EDV、ESV增大，心功能指标EF、FS一下降，室 间隔收缩期与舒张期厚度变薄，左房增大(P<0.05，0.01)。2、大面积胡I大鼠2周与8周时心脏结构与功能对照分析 大面积AMI大鼠8周时较2周时心脏的结构及功能的改变:IVSd下降(P<0.01)。EDD、ESD、EDV、ESV增加，FS、EF卜降，LA增大，IVSs卜降，LVPW%增大(P<0.05)。二、正常大鼠与大面积AMI人鼠更多还原

【Abstract】 PrefaceCHD is one of heart diseases, which influence people’s health seriously, so early diagnosis, evaluation of severity, and early treatment of CHD are very important. AMI is one of the most common causes of heart failure and death in human as emergency of CHD. Animal experiment plays an important role in evaluating of cardiac function of myocardial infarction. Rat can be used as an excellent animal model with the development of trans-gene technique because rat is cheap and easily obtained, and the gene of rat is similar with human. Researchers need a means to examine and evaluate quickly the cardiac structure and function of rat. Cardiac examination non-invasively plays an important role in vivo-evaluation of these small animals. High frequency echocardiography, MR1 and CT can be used to evaluate non-invasively left ventricular morphology, structure, and function of rat. MRI and CT, which are limited by high price and complicated operation, are not preferred. High frequency echocardiography can evaluate left ventricular morphology, structure, function, and flow of AMI rat. De Simome and Pfeffer began to evaluate cardiac structure and function of rat with echocardiography in 1990.But there is little research about which echocardiographic index can be used to evaluate the cardiac structure and function of rat. The change of cardiac structure and function of rat in different phases of AMI is seldom reported in literature. DTI pulse wave technique (DTI-PW) has been proved a good index to evaluate myocardial movement and left ventricular function in human. Whether DTI-PW can be used to evaluate segmental myocardial movement and function of rat is seldom reported. We explore by the control research between normal and AMI rat in different phases: How to evaluate AMI rat with echocardiographic index and the process of left ventricular remodeling of AMI rat in different phases; whether DTI-PW can be used to evaluate segmental myocardial movement and function of rat.ObjectiveTo explore the value of High frequency echocardiography and DTI-PW to evaluate cardiac structure and function and myocardial movement of Sprague-Dawley Rat models with AMI.MethodsProduction of Rat Models with Acute Myocardial InfarctionSprague-Dawley rats were anesthetized and intubated and ventilated with ventilator. Through a thoracotomy on the left side, Left anterior descending coronary artery was ligated proximally. Infarct area no less than 30% was large, and infarct area less than 30% was mild or moderate. Study Designs1. Evaluation of cardiac structure and function of AMI rat A) Comparison of AMI rats of different infarct areaCardiac structure and function of normal and AMI rats were examined with high frequency echocardiography in 2 weeks or 8 weeks after induction successfully. Normal and mild/moderate infarct and large infarct group rats were divided by infarct area, which was ascertained by Masson trichrome staining. The cardiac structure and function of three groups were compared. B Comparison of AMI rats of the large infarct area in different phasesCardiac structure and function of AMI rats were examined with high frequency echocardiography in 2 weeks and 8 weeks after induction successfully. Infarct area was ascertained by Masson trichrome staining. The cardiac structure and function in 2 weeks and 8 weeks of large infarct rats were compared.2. Comparison of myocardial movement and mitral valve orifice flow between normal and large infarct ratsThe left ventricular anterior and posterior wall myocardial movement of normal and AMI rats were examined with high frequency echocardiography and DTI in 8 weeks after induction successfully. Mitral valve orifice flow velocity was recorded by Doppler flow imaging. Infarct area was ascertained by Masson trichrome staining. Mitral orifice flowvelocity and myocardial movement were compared between the normal and the large infarct rats. 3. Reproducibility and variability analysisNormal rats were examined with high frequency echocardiography and DTI in更多还原