心力衰竭是一种机制独特而复杂的病理生理过程，也是许多疾病终末期的共同通路。来源于动物模型的研究为认识其机制提供了大量的资料。大鼠因为其对实验的耐受性好，心脏的解剖生理与人类类似等多方面优点成为研究心衰的实验动物的首选。 心功能下降是心力衰竭病理生理过程中一个非常重要的环节，心功能的变化能反映药物疗效、能评估疾病的预后等，是评价心衰程度的重要指标。超声心动图快速、方便、无创、可重复测量，在心功能评价方面有独到的优点，近年来随着多普勒组织成像技术的发展，多种超声新技术应运而生，成为评价心脏舒缩功能和心室重构等的新指标。 心室重构是心肌梗死后充血性心力衰竭进展的关键步骤，基质金属蛋白酶通过对细胞外基质的降解在心肌重构中起重要作用。因此本实验从超声和基础两方面探索心肌梗死后心力衰竭大鼠心肌收缩功能及心室重塑机制的变化规律，为定量评估心衰后心功能改变提供新的思路和实验依据。 第一部分 超声研究 目的：应用定量组织速度成像(QTVI)、组织追踪成像(TTI)技术及应用应变(SI)、应变率成像(SRI)技术定量评价心肌梗死后心力衰竭大鼠心肌局部收缩功能的改变，为心肌梗死后心功能的研究提供理论依据。 方法：选用体质量约200-220g的2月龄雄性SD大鼠70只，随机分为4组，手术4周(25只)及手术8周组(25只)：麻醉后行开胸术，打开心包，结扎左冠状动脉前降支；假手术组(10只)：同样开胸，打开心包，但不结扎；正常组(10只)：不予任何处理。术后每日观察大鼠的精神状态等一般情况的变化。术前1天、术后4周末及术后8周末均行超声心动图检查，应用组织速度成像、组织追踪成像技术及应变、应变率成像技术定量评价心肌局部收缩功能的改变；测量结果行重复性及差异度分析。 结果：①术后存活大鼠在术后第10天左右均出现明显心衰体征。 ②与正常组及假手术组相比，手术4周组左室短轴缩短率(FS)及射血分数(EF)均下降(P<0.05)；手术8周组左室内径指数(LV指数)增大、左室后壁指数(LVPW指数)及室间隔指数(IVS指数)均减小(P<0.05)， FS及EF均下降(P<0.01)，其中手术8周组FS及EF值较手术4周组明显减低(P<0.05)。③正常组与假手术组相应节段之间的收缩期峰值速度(Vs)无明显差异。手术4周组左室前壁及后间隔的基底段、中间段、心尖段、侧壁的中间段、心尖段的Vs明显小于正常组及假手术组相应室壁节段的Vs，差异有统计学意义(P<0.05)，而下壁基底段、中间段、心尖段、侧壁基底段的Vs与正常组及假手术组比，差异无统计学意义(P>0.05)，但有下降趋势。手术8周组第8周末大鼠左室壁所有节段的Vs小于手术4周组第4周末相应节段的Vs (P<0.05)。④正常组与假手术组相应节段之间的收缩期最大位移(Ds)无明显差异。手术4周组第4周末左室前壁及后间隔的基底段和中间段的Ds明显小于正常组及假手术组相应室壁节段的Ds(P<0.05)，而下壁及侧壁的基底段和中间段的Ds与正常组及假手术组比，差异无统计学意义(P>0.05)，但有下降趋势。手术8周组中，所有节段的Ds较手术4周组相应节段的Ds明显下降(P<0.05)。⑤与正常组及假手术组相比，除下壁中间段及基底段外，手术组各节段收缩期峰值应变(Ssys)、收缩期峰值应变率(SRsys)、收缩末期应变均明显下降(P<0.05)，其中手术8周组前壁基底段、中间段及侧壁基底段各指标值较手术4周组明显下降(P<0.05)；与正常组及假手术组相比，除下壁中间段及基底段外，手术组各节段收缩后应变指数(PSI)升高(P<0.05)，其中手术8周组前壁基底段、中间段及侧壁基底段较手术4周组明显升局(P<0.05)。⑥所有指标研究者内及研究者间差异度均<20%。 结论：通过结扎大鼠左冠状动脉前降支，可以成功复制心肌梗死后心力衰竭大鼠模型。应用QTVI、TTI技术及SI、SRI技术以不同方法从左室长轴方向上定量评价心肌梗死后心力衰竭大鼠心肌局部收缩功能的改变，反映心室重塑程度。各指标测量有较好的重复性。 关键词 定量组织速度成像，组织追踪成像，应变，应变率，心肌梗死 第二部分 基础研究 目的：观察心肌梗死后心衰大鼠心肌形态结构以及胶原容积分数的变化，检测各组大鼠心肌MMP-2、MMP-9蛋白及mRNA的表达，并探索其表达与心肌梗死后心力衰竭大鼠心肌重构进展的关系。 方法：实验动物及分组方法同第一部分。于术后每日观察大鼠精神状况等一般情况的变化；于4周末及8周末处死大鼠，测量大鼠全心重量指数及左室重量指数；取大鼠心脏心肌组织行HE染色及Masson染色，观察其光镜下形态结构并测定胶原容积分数；采用Western blot法及RT-PCR法分别检测各组大鼠心肌MMP-2、MMP-9蛋白及mRNA表达。 结果：①术后存活大鼠在术后第10天左右均出现明显心衰体征。②与正常组及假手术组相比，手术4周组及手术8周组大鼠体重校正的全心重量指数(THMI)及左室重量指数(LVMI)明显升高(P<0.05)，其中手术8周组THMI及LVMI较手术4周组明显升高(P<0.05)。③与正常组及假手术组相比，手术4周组及手术8周组光镜下心肌纤维化程度较重，且手术8周组较手术4周组更明显。 ④与正常组及假手术组相比，手术4周组及手术8周组大鼠心肌胶原容积分数(CVF)明显升高(P<0.05)，与手术4周组相比，手术8周组CVF明显升高(P<0.05)。⑤正常组及假手术组仅表达少量的MMP-2和MMP-9，手术4周组及手术8周组大鼠MMP-2及MMP-9的蛋白及mRNA表达较正常组及假手术组明显升高，其中手术8周组MMP-2的蛋白及mRNA的表达低于手术4周组，而MMP-9的蛋白及mRNA的表达高于手术4周组。 结论：在术后8周内随着心肌梗死后心力衰竭的进展，心肌胶原过度沉积，心肌僵硬度增加，心腔进行性扩大，心功能进行性恶化；心肌组织基质金属蛋白酶MMP-2、MMP-9蛋白及mRNA表达水平上调，并参与了心室重构的进程。 关键词 心肌梗死，左室重量指数，全心重量指数，胶原容积分数，基质金属蛋白酶

 Heart failure is a complicated pathophysiologic process, and is a common pathway at the end stage of many diseases. Researches based on heart failure animal models provided abundant information of its mechanism. Rat model become the most common choice of heart failure animal models, for many advantages such as good tolerance to experiment, the similarity in heart anatomy and physiology. The falling of heart function is a very important step in the pathophysiologic process of heart failure. The heart function is the most important index to evaluate the extent of heart failure; its variation can reflect the pharmacological effect of medicine, and make a prognosis of heart failure patient. Echocardiography has its specific advantages in the evaluation of heart function, for it is a convenient, noninvasive and repeatable way. Along with the development of Tissue Doppler Imaging technology, several new technologies emerge and become new methods to evaluate the systolic and diastolic heart function and ventricular remodeling. Ventricular remodeling is the key process in development of congestive heart failure post infarction. Matrix metalloproteinases play an important role in the remodeling of myocardium via degradation of extracellular matrix. Thus, the variation in systolic function and ventricular remodeling of post-infarction heart failure rats are studied in this research in two aspects: ultrasonic research and experimental research. This research provides new thoughts and experimental evidences for the quantitative evaluation of heart function post heart failure. Part 1: Evaluating systolic function of post-infarction heart failure rats by echocardiographic imaging technology Objective: Apply quantitative tissue velocity imaging (QTVI), tissue tracking imaging (TVI), strain imaging (SI) and strain rate imaging (SRI) to evaluate variation in regional myocardial systolic function quantitatively in post-infarction heart failure rat model. Provide theoretical evidence for researches in heart function post infarction. Methods: 70 2-month-old male SD rats (body mass 200-220g) were randomly divided into 4 groups: operation group was divided into 2 groups: 4 weeks group and 8 weeks group, including 25 rats in each group o Each group underwent thoracotomy and ligation of anterior descending branch of left coronary artery; sham operation group, including 10 rats, underwent thoracotomy without ligation of coronary artery; control group, including 10 rats, did not receive any treatment. General healthy states of rats were observed every day. Echocardiography technologies, including QTVI, TTI, SI and SRI, were used to evaluate variations in regional systolic function quantitatively in three time point: one day before surgery, the end of the 4th week and the end of 8th week after surgery. Repeatability and variance of all results were analyzed. Result: ①Obvious heart failure symptoms were observed in survived rats in operation group about 10 days after surgery. ②Compared with control group and sham operation group, fraction shortening (FS) and ejection fraction (EF) decreased significantly in 4 weeks group (P＜0.05)and 8 weeks group (P＜0.01). FS and EF were significantly lower in the 8 weeks group than 4 weeks group (P＜0.05). Left ventricle index (LV) was increased, left ventricle posterior wall index (LVPW) and interventricular septum index (IVS) were decreased in 8 weeks group (P＜0.05). ③No significant differences in systolic peak velocity (Vs) were found between corresponding segments in control group and sham operation group. Vs in basal, middle, apical segments of anterior and septal wall, middle and apical segments of lateral wall were significantly lower in 4 weeks group than corresponding segments in control group and sham operation group(P＜0.05). Vs in basal, middle and apical segments of inferior wall, basal segments of lateral wall were lower in 4 weeks group than that in control group and sham operation group, but there were no significances(P＞0.05). Vs in all segments of left ventricle were significantly lower in 8 weeks group than corresponding segments in 4 weeks group(P＜0.05). ④No significant differences in systolic peak displacement (Ds) were found between corresponding segments in control group and sham operation group. Ds in basal, middle segments of anterior and septal wall were significantly lower in 4 weeks group than corresponding segments in control group and sham operation group(P＜0.05). Ds in basal, middle segments of inferior and lateral wall were lower in 4 weeks group than corresponding segments in control group and sham operation group, but there were no significances(P＞0.05). Ds in all segments of left ventricle were significantly lower in 8 weeks group than corresponding segments in 4 weeks group(P＜0.05). ⑤Except for basal and middle segments of inferior wall, peak of strain in systolic(Ssys), peak of strain rate in systolic(SRsys) and strain in end systolic in all segments in operation group were significantly lower than corresponding segments in control group and sham operation group(P＜0.05). These three indexes in basal and middle segments of anterior wall, basal segments of lateral wall were significantly lower in 8 weeks group than corresponding segments in 4 weeks group(P＜0.05). Except for middle and basal segments of inferior wall, post-systolic strain index (PSI) in all segments in operation group were significantly higher than corresponding segments in control group and sham operation group (P＜0.05). PSI in basal, middle segments of anterior wall, basal lateral wall in 8 weeks group were significantly higher than corresponding segments in 4 weeks group(P＜0.05).⑥Variances in all indexes within researchers or between researchers were lower than 20%. Conclusion: Post-infarction heart failure rat model can successfully be formed by ligation of descending branch of left coronary artery. Echocardiography technologies such as QTVI, TTI, SI and SRI, in different aspects, can evaluate the variation of regional myocardial systolic function quantitatively in long-axis of the left ventricle in post-infarction heart failure rat model; also, it can reflect the extent of ventricular remodeling. The repeatability of these technologies is well. Key words Quantitative tissue velocity imaging, Tissue tracking imaging, Strain and strain rate, Myocardial infarction Part 2: Research on the possible mechanism of ventricular remodeling of post-infarction Objective: Observe the variation in myocardium morphology and collagen volume fraction (CVF) in post-infarction heart failure rats. Detect MMP-2, MMP-9 expression in each group in protein level and mRNA level. Explore the relationship between MMP expression and the progression in myocardium remodeling in post-infarction heart failure rats. Methods: Experimental animals and their groups were the same as research in part one. General health states of rats were observed everyday. Rats were killed at the end of 4 weeks and at the end of 8 weeks. Myocardium tissues were stained by HE and Masson stain, myocardium morphology was observed under microscope and collagen volume fraction was measured. MMP-2 and MMP-9 protein expression in each group were analyzed by Western blot, and their mRNA expressions were analyzed by RT-PCR. Result:①. Obvious heart failure symptoms were observed in survived rats in operation group about 10 days after surgery.②. Compared with rats in control group and sham operation group, Total heart mass index (THMI) and left ventricular mass index (LVMI) in 4 weeks group and 8 weeks group were significantly increased(P＜0.05). THMI and LVMI in 8 weeks group were higher than 4 weeks group (P＜0.05).③. Compared with rats in control group and sham operation group, severe myocardium fibrosis was found under microscope in operation groups, especially in 8 weeks group.④. Compared with rats in control group and sham operation group, CVF in 4 weeks group and 8 weeks group were significantly increased(P＜0.05). CVF in 8 weeks group were higher than in 4 weeks group (P＜0.05).⑤. Only few MMP-2 and MMP-9 expression were detected in control group and sham group. MMP-2 and MMP-9 expression in protein level and mRNA level were higher in 4 weeks group and 8 weeks group than in control group and sham operation group. MMP-9 expression in protein and mRNA level was higher in 8 weeks group than 4 weeks group, in contrary, MMP-2 expression was lower in 8 weeks group than 4 weeks group. Conclusion: Along with the progression of heart failure post infarction in 8 weeks after operation, collagen over accumulation, increased myocardium stiffness, dilated ventricle and gradually deteriorated heart function were detected in operation groups. MMP-2 and MMP-9 expression were up regulated in myocardium in protein level and mRNA level, both MMP-2 and MMP-9 took part in the progression of ventricular remodeling. Key words Myocardial infarction, Left ventricular mass index, Total heart mass index, Collagen volume fraction, Matrix metalloproteinase