骨髓间充质干细胞移植显著促进急性心肌梗死大鼠的心功能恢复

目的通过横向比较乳鼠心肌细胞、骨髓单个核细胞（BMMNCs）、骨髓间充质干细胞（BMMSCs）移植治疗大鼠急性心肌梗死（MI）的疗效,确定更优异的移植细胞。方法以结扎法建立大鼠急性MI模型,分离培养乳鼠心肌细胞、BMMNCs、BMMSCs,体外进行DAPI标记后,直视下分别植入急性MI 1周后的大鼠MI中心及边缘区,移植的细胞数为2×106/只。移植后4周,进行后心功能检测,并处死动物以免疫组化染色法检测移植细胞的分化及血管新生。结果LSD法检测显示,大鼠的左室射血分数（LVEF）,BMMSCs移植组为（61.00±2.21）%、乳鼠心肌细胞移植组为（58.74±2.21）%、BMMNCs移植组为（59.87±3.05）%较对照组[为（55.45±3.05）%]大鼠的心功能均有显著提高（P值依次为<0.05、<0.05、<0.01）其中BMMSCs组优于其他处理组,BMMSCs能表达血管平滑肌肌动蛋白,促进血管新生,但未见其表达心肌细胞的特异抗原。结论在分别以乳鼠心肌细胞、BMMNCs和BMMSCs移植治疗大鼠的急性MI的比较中,BMMSCs对心功能的保护效果最显著,保护机制与其血管新生等有关。     

微环境预处理的骨髓间充质干细胞治疗大鼠心肌梗死

目的 观察骨髓间充质干细胞(BMSC)或经预处理分化的BMSC(induced BMSC,iBMSC)移植能否改善心肌梗死大鼠的心功能.方法雄性SD大鼠32只(250～300 g),分为假手术组、磷酸缓冲液(PBS)注射组、BMSC移植组和iBMSC移植组共4组,每组8只.将分离的BMSC与心肌细胞(微环境)共培养2周进行预分化,大鼠心肌梗死模型建立1周后,将BMSC或iBMSC细胞悬液注入梗死区的边缘位置.分别于细胞移植后的第1、2和4周,超声心动图检测各组大鼠心脏的左心室射血分数(LVEF),左心室舒张末期内径(LVIDd),左心室收缩末期内径(LVIDs)及短轴缩短率(FS).移植后第4周进行组织学观察,心脏组织石蜡包埋切片后采用免疫荧光技术检测移植细胞的示踪标记物及心肌标志蛋白的表达情况.结果iBMSC组LVEF在第4周时是(77.3±2.6)%,与假手术组(81.8±3.6)%比较差异无统计学意义(P＞0.05),而PBS组及BMSC组的LVEF值均低于假手术组(P均＜0.05).PBS组FS移植前后没明显变化,iBMSC组FS从移植前的(24.1±3.9)%上升到第4周的(45.1±3.1)%.M型超声心电图显示iBMSC治疗组左心室收缩能力较细胞移植前明显改善.免疫荧光分析显示,SPIO标记的移植细胞在体内表达心肌细胞标志蛋白α-辅肌动蛋白和缝隙连接蛋白43.结论经过微环境预处理的BMSC较未处理的干细胞改善心功能效果更好.这一研究为干细胞的改造与细胞移植修复心肌梗死提供了强有力的证据.     

用三七总皂苷与卡维地洛治疗AMI后大鼠改善心功能作用的疗效比较与评价

目的研究三七总皂苷与卡维地洛对心肌梗死后大鼠左室心功能改善作用的疗效并比较评价。方法手术法结扎左冠状动脉前降支建立SD大鼠AMI模型36只,将模型鼠随机分为心梗对照组（AMI组）,三七总皂苷治疗组(PNS组,80 mg·kg^-1·d^-1)和卡维地洛治疗组(CARV组,6 mg·kg^-1·d^-1),每组12只;另设假结扎组（Sh组,12只）。术后24小时开始灌胃给药,4周后对各组大鼠进行超声心动图心功能和血浆脑钠肽（NT-proBNP）浓度检测。结果 （1）与Sh组比较,AMI组左室射血分数（EF）和左室收缩百分率（FS）、室间隔舒张、收缩末期厚度（IVSd、IVSs）与左室前壁收缩末期厚度（LVAWDs）均明显降低（P<0.01）,左室舒张、收缩末期内径（LVIDd、LVIDs）显著增加,且左室后壁收缩末期厚度（LVPWDs）明显增加（P<0.05）。而二尖瓣血流E/A比值下降明显;心肌运动应变率（Radial Strain Rate）减小,达峰时间（TPK,ms）明显延长;NT-proBNP浓度显著增高（P<0.01）。（2）与AMI组比较,PNS组和CARV组的EF、FS、IVSd、IVSs与LVAWDs明显增加,而LVIDd、LVIDs和LVPWDs明显降低（P<0.01）;且心肌运动应变率明显增加,达峰时间明显缩短;NT-proBNP浓度明显降低。（3）PNS组与CARV组比较,PNS组的EF、FS和LVAWDs增加显著,LVIDd、LVIDs减小明显;而IVSd、IVSs、和LVPWDs无明显差异（P>0.05）。并且,PNS组的二尖瓣血流E峰、A峰和E峰下降速率均明显增大（P<0.05）,而E/A比值和心肌应变率、达峰时间与NTproBNP浓度两组无明显差异。结论心肌梗死后大鼠的左心室收缩和舒张功能异常严重;用三七总皂苷和卡维地洛治疗4周后均能明显改善其心功能,防止心衰;但PNS在提高EF、LVAWDs和二尖瓣血流方面更优于卡维地洛。     

用三七总皂苷与卡维地洛治疗AMI后大鼠改善心功能作用的疗效比较与评价

目的研究三七总皂苷与卡维地洛对心肌梗死后大鼠左室心功能改善作用的疗效并比较评价。方法手术法结扎左冠状动脉前降支建立SD大鼠AMI模型36只,将模型鼠随机分为心梗对照组（AMI组）,三七总皂苷治疗组(PNS组,80 mg·kg^-1·d^-1)和卡维地洛治疗组(CARV组,6 mg·kg^-1·d^-1),每组12只;另设假结扎组（Sh组,12只）。术后24小时开始灌胃给药,4周后对各组大鼠进行超声心动图心功能和血浆脑钠肽（NT-proBNP）浓度检测。结果 （1）与Sh组比较,AMI组左室射血分数（EF）和左室收缩百分率（FS）、室间隔舒张、收缩末期厚度（IVSd、IVSs）与左室前壁收缩末期厚度（LVAWDs）均明显降低（P<0.01）,左室舒张、收缩末期内径（LVIDd、LVIDs）显著增加,且左室后壁收缩末期厚度（LVPWDs）明显增加（P<0.05）。而二尖瓣血流E/A比值下降明显;心肌运动应变率（Radial Strain Rate）减小,达峰时间（TPK,ms）明显延长;NT-proBNP浓度显著增高（P<0.01）。（2）与AMI组比较,PNS组和CARV组的EF、FS、IVSd、IVSs与LVAWDs明显增加,而LVIDd、LVIDs和LVPWDs明显降低（P<0.01）;且心肌运动应变率明显增加,达峰时间明显缩短;NT-proBNP浓度明显降低。（3）PNS组与CARV组比较,PNS组的EF、FS和LVAWDs增加显著,LVIDd、LVIDs减小明显;而IVSd、IVSs、和LVPWDs无明显差异（P>0.05）。并且,PNS组的二尖瓣血流E峰、A峰和E峰下降速率均明显增大（P<0.05）,而E/A比值和心肌应变率、达峰时间与NTproBNP浓度两组无明显差异。结论心肌梗死后大鼠的左心室收缩和舒张功能异常严重;用三七总皂苷和卡维地洛治疗4周后均能明显改善其心功能,防止心衰;但PNS在提高EF、LVAWDs和二尖瓣血流方面更优于卡维地洛。     

经冠状动脉移植自体BM-MNCs治疗猪急性心肌梗死的作用

目的探讨冠状动脉内移植自体骨髓单个核细胞（BM—MNCs）治疗猪急性心肌梗死的有效性。方法实验动物分为冠脉内移植MNCs组（n=6）及冠脉对照组（n=5）。冠脉内移植BM—MNCs后4周观察移植细胞归巢情况、小血管密度、心功能变化。结果冠脉内MNCs移植后4周,心肌细胞间可见发蓝色荧光的移植细胞,散在分布,心肌细胞间有较多新生毛细血管并可见新生的心肌样细胞。移植组小血管密度、左室射血分数（LVEF）及短轴缩短率（FS）明显高于对照组（P〈0．01）,左室舒张末期内径（LVEDd）低于对照组（P〈0．05）。结论经冠脉移植的BM—MNCs可归巢到宿主心肌,有促进缺血心肌血管新生、改善左室收缩功能、减轻心室重构的作用。     

心肌内移植自体骨髓单个核细胞治疗急性心肌梗死的实验研究

目的探讨心肌内移植自体骨髓单个核细胞(BM-MNCs)治疗猪急性心肌梗死的有效性和安全性。方法11只小型猪分为两组:BM-MNCs组(n=6)和对照组(n=5)。心肌内移植BM-MNCs后4周观察移植细胞归巢情况、小血管密度、心功能及冠脉侧支血管形成情况及可能发生的不良反应。以超声心动图评价心室结构及功能变化。结果心肌内MNCs移植后4周心肌细胞间可见发蓝色荧光的移植细胞,心肌细胞间有较多新生毛细血管并可见新生的心肌样细胞。移植组小血管密度、左室射血分数(LVEF)及短轴缩短率(FS)明显高于对照组(P<0.01)而左室舒张末期内径(LVEDd)低于对照组(P<0.05)。移植组冠脉侧支循环形成较对照组明显。心肌内移植MNCs没有发现异常增生、钙化或肿瘤形成。结论心肌内移植BM-MNCs有较多的移植细胞归巢到宿主心肌,有助于促进缺血心肌血管新生,有改善左室收缩及舒张功能,减轻心室重构的作用。     

辛伐他汀对高脂血症大鼠心肌梗死后心室重构的影响

目的研究高脂血症对心肌梗死(AMI)后心室重构的影响,以及辛伐他汀对心梗大鼠心室重构的作用。方法高脂饲料喂养SD大鼠15d后结扎冠脉,造成高脂血症心肌梗死复合模型,分为假手术组、心梗组、高脂假手术组、高脂心梗组、辛伐他汀大剂量和小剂量共6组,术后48h给药,观察48h和4周死亡率,高频超声心动图于术后4周观察心脏结构功能及梗死心肌范围。结果高脂组大鼠AMI后48h死亡率高于正常血脂AMI组(P<0.05)。术后4周高脂假手术组较正常血脂假手术组FS降低(P<0.05);且血清TC、LDL-C水平分别与FS、EF和LVDs呈直线相关(P<0.01)。辛伐他汀大、小剂量均能降低LVDd、LVDs(P<0.05,0.01),降低LVEDV、LVESV(P<0.01),升高EF、FS(P<0.05)。结论高脂血症能损害心功能,增加AMI后急性期死亡率,高脂AMI动物较正常血脂AMI动物心室重构和心功能损伤均有加重趋势。辛伐他汀不仅降低血脂水平,还可减轻心室扩张,改善心功能。     

人脂肪间充质干细胞治疗大鼠急性心肌梗死的实验研究

目的:探讨人脂肪间充质干细胞(HADMSCs)移植于大鼠缺血心肌后的增殖分化情况及心功能改善情况。方法:通过结扎法建立心肌梗死模型,1周后将BrdU标记的HADMSCs通过经心外膜注射至心梗移植组梗死心肌,行超声心动图检查。建模后5周行HE染色观察心肌梗死情况,TTC染色计算左室梗死面积百分比,免疫组织化学检测HADMSCs移植后的存活和分布情况及心肌特异性蛋白的表达。结果:超声检查心梗移植组左心室收缩末期内径、舒张末期内径均小于心梗对照组,而射血分数均大于心梗对照组(P0.05);TTC染色结果显示心梗移植组左室梗死面积百分比[(23.6±4.3)%]小于心梗对照组左室梗死面积百分比[(32.4±5.6)%](P0.05)。心肌组织免疫组织化学结果显示带有BrdU标记的移植细胞在心梗周边区域存活,且特异性肌钙蛋白呈阳性表达。结论:HADMSCs能够在大鼠梗死心肌内存活,并分化为心肌样细胞,减小梗死面积,改善心功能。     

动员自体骨髓干细胞对急性心肌梗死大鼠心功能的影响

目的:探讨联合应用粒细胞集落刺激因子（G-CSF）和干细胞因子（SCF）动员心肌梗死大鼠的骨髓干细胞并观察对心功能的影响及探讨其可能机制。方法:雄性W istar大鼠40只经结扎冠状动脉前降支制作心肌梗死模型后随机分为两组。①动员组:皮下注射rh-CSF和rh-SCF。②对照组:皮下注射等量生理盐水。28 d后通过测定血流动力学观察大鼠心功能变化,通过伊文氏蓝-TTC染色方法观察心肌梗死范围的变化。通过HE染色方法、免疫荧光标记染色和双重免疫荧光标记染色观察心肌梗死范围内心肌纤维化、血管和心肌再生的变化。结果:动员组心肌组织梗死范围内成纤维细胞增生程度轻,新生血管和心肌细胞的特异蛋白染色阳性,与对照组比较,动员组左室收缩压显著增大（P<0.05）,舒张末压显著减小（P<0.05）,左室压上升/下降变化最大速率显著增快（P<0.05）。动员组的缺血范围和心肌梗死的范围比对照组均有所缩小（P<0.05）。结论:G-CSF和SCF动员骨髓干细胞可以改善心肌梗死后大鼠的心功能。     

自体骨髓间充质干细胞移植对急性心肌梗死后心功能的影响

目的观察骨髓间充质干细胞（MSCs）经冠脉移植对急性心肌梗死后心功能的影响。方法24只日本大耳白兔,随机分为MSCs移植组（n=12）和培养液对照组（n=12）。从兔股骨抽取骨髓,体外培养MSCs。通过结扎左冠前降支建立急性心肌梗死模型。冠脉结扎后7d,细胞移植组和对照组直接经冠脉注入MSCs和培养液。于心肌梗死前、细胞移植前、细胞移植后1、2和4周对兔进行超声心动图检查。移植后4周处死动物,进行BrdU和第Ⅷ因子相关抗原免疫组化检测。结果移植后2周,MSCs移植组在射血分数（LVEF）和左室收缩末直径（LVESD）方面与移植前和对照组相比有显著改善（P<0.05）;移植4周后,LVEF、LVESD和左室舒张末直径（LVEDD）在MSCs移植组与移植前及对照组相比均有显著改善（P<0.05）。免疫组化检测发现,MSCs移植组BrdU染色阳性,血管计数较对照组明显增多（P<0.01）。结论经冠脉移植的MSCs可在梗死区心肌内存活并逐渐分化成心肌样细胞,促进毛细血管生成,显著改善心功能。     

Effects of myocardial hypoxia and ischemia on myocardial scintigraphy

The effect of regional myocardial ischemia and hypoxia on myocardial scintigraphy was studied in patients and dogs after intravenous administration of cesium-129. Seven men with angiographically proved ischemic heart disease underwent exercise testing and ¹²⁹Cs was given immediately when ischemia was manifested in the electrocardiogram. Defects were not evident in the scintigrams of any patient. Failure to visualize a defect might be related to delayed uptake of ¹²⁹Cs by the myocardium (maximal uptake in 45 minutes). The ischemic state was dissipated before the disparity in uptake between normal and ischemic myocardium could be visualized. Cesium-129 is useful for identifying acute myocardial infarcts but should not be used to visualize transient exercise-induced regional ischemia.Six dogs were given ¹²⁹Cs after induction of regional myocardial hypoxia by perfusion of the anterior descending coronary artery with venous blood. In each, scintigraphy revealed a defect that resolved after reperfusion with arterial blood. Two other dogs were given ¹²⁹Cs before perfusion with hypoxemic blood; neither dog manifested a defect. Since perfusion was maintained by a pump these results suggest that the major cause of the scintigraphically observed defect was inadequate cellular uptake of ¹²⁹Cs rather than excessive cellular loss. Since regional myocardial hypoxia produced a reversible defect, scintigraphic studies might overestimate the size of an acute myocardial infarct in man by including the ischemic zone surrounding the infarct.     

Diagnosis and prevention of myocardial reperfusion injury in experimental myocardial infarction

In an experimental study in 69 dogs with the occluded anterior descending branch of the left coronary artery, dibunol, an antioxidant, and isoptin, a Ca2+ antagonist reduced myocardial infarction area, prolonged survival time and brought down mortality rate, in spite of an increase in reperfusion-related arrhythmias. The value of various electrocardiographic parameters for the diagnosis of ischemized-myocardium reperfusion and the severity of reperfusion-related heart damage in relation to the type of preventive medication, as compared to postmortem findings, are discussed.     

Assessment of myocardial blood flow and volume using myocardial contrast echocardiography

The development of new microbubble agents and ultrasound imaging modalities now allows the assessment of myocardial perfusion with echocardiography. Microbubbles also can be administered intravenously as constant infusions, which allows their concentration in blood to reach steady state. If the relation between microbubble concentration and video intensity is within the linear range, then myocardial video intensity will reflect the concentration of microbubbles in that region, which at steady state is the myocardial blood volume. The ability to destroy microbubbles and measure their replenishment into the ultrasound beam provides an opportunity to evaluate microbubble (or red blood cell) velocity. The product of myocardial blood volume and red blood cell velocity represents myocardial blood flow.     

Silent ischemia and loss of reversible myocardial dysfunction following myocardial infarction

Sixty-seven asymptomatic patients were enrolled after a first uncomplicated myocardial infarction (MI) so as to study the relevance of reversible myocardial dysfunction in determining left ventricular function soon after the acute episodes and 12 months later. Moreover, the potential role of silent ischemia in conditioning the evolutive aspects of contractile dysfunction has been investigated. Postextrasystolic potentiation during two-dimensional echocardiographic (2-D echo) monitoring has been used to detect the presence of viable myocardium in asynergic myocardial segments. Results of electrocardiographic (ECG) ambulatory monitoring at predischarge determined patient groups: Group A included 49 patients without ST changes during monitoring, while Group B included 18 patients with silent ischemia. Incidence of reversible myocardial dysfunction was similar in the two study groups (82 vs. 86%, p = NS). Group B patients were older (59.6 ± 6.7 vs. 50.6 ± 10.6 years, p < 0.015) and had lower ejection fractions (EFs, 43.4 ± 6.4% vs. 51.2 ± 8.3%, p = 0.026) and higher at-rest wall-motion scores (WMSs, 11.4 ± 5.9 vs. 7.2 ± 3.8, p = 0.019). Left ventricular end-diastolic volume (LVEDV) and potentiated WMS did not differ. At 1-year examination, Group B patients exhibited a greater LVEDV index (96 ± 6.5 vs. 70.7 ± 14 ml/m², p < 0.002) with a worsening both in rest and in potentiated wall-motion score index (12.8 ± 4.6 vs. 5.3 ± 1.8, p < 0.001; 9.2 ± 3.6 vs. 4.8 ± 2.2, p < 0.001, respectively). Left ventricular EF remained significantly depressed in Group B patients (42 ± 8.7% vs. 55.5 ± 8.1%, p < 0.002). Over the first year, spontaneous functional recovery of asynergic segments occurred in 60% of Group A patients with reversible myocardial dysfunction at early study. In Group B patients, only three (20%) showed functional recovery, and a small number (24%) maintained reversible contractile dysfunction. Thus, reversible contractile dysfunction is a common finding in asymptomatic patients without clinical ischemia soon after a first MI. The presence of silent ischemia during ambulatory ECG monitoring identifies a group of patients at high risk of further loss of myocardial viability and progressive left ventricular dilation over the first year.     

炎症在梗死心肌损伤与修复中的作用

炎症在心肌梗死后心肌损伤与修复中扮演着重要的角色,其中Ly6C~(Lo)单核细胞、M2巨噬细胞及CC类趋化因子受体2(CCR2)阴性巨噬细胞可能有助于心肌梗死后心肌再生修复。同时,心肌梗死后单核/巨噬细胞释放大量的炎症因子,如白细胞介素-1β(IL-1β)、IL-6、肿瘤坏死因子-α(TNF-α)、IL-10、CCR2等,它们也发挥重要作用。研究已经表明心肌梗死后强烈的炎症反应是造成心肌组织继发性损伤的重要因素,因此通过药物等外界手段抑制心肌梗死后的炎症反应,减轻心脏损伤,保护心肌组织,可能会为心肌梗死后的心肌再生修复提供新的策略。     

Biochemical markers of myocardial necrosis in acute myocardial infarction and thrombolysis

This paper summarizes the most important biochemical properties of several biochemical markers of myocardial injury and discusses the practical applications of these markers for the diagnosis of acute myocardial infarction, for the noninvasive detection of coronary artery recanalization after treatment with thrombolytic agents, and for the early identification of cardiovascular events in unstable angina.     

Remodeling of myocardial interstitium in left ventricular hypertrophy and myocardial infarction

Structural and biochemical modifications of the myocardium (remodeling) occur during the development of left ventricular hypertrophy and acute myocardial infarction. An important part of this process of myocardial remodeling occurs in the interstitial compartment. The myocardial interstitium is composed mainly of fibrillar collagen. These changes are associated to modifications in ventricular function that could be deleterious and have clinical manifestations. Some salutory effects of the treatment of both conditions are related to modifications of the process of myocardial interstitial remodeling.     

早期心肌再梗塞和梗塞延展的发生因素和心电图特征

２１２例急性心肌梗塞中，２１例发生早期心肌再梗塞和梗塞延展，发生率为９．９％（２１／２１２），多发生在梗塞后２～８ｄ．高危因素有：各种部位的前壁心肌梗塞，梗塞后心绞痛，心功能Ｋｉｌｌｉｐ分级Ⅱ级以上，大、小便用力及活动增加等．早期心肌再梗塞和梗塞延展的心电图特征为：ＳＴ段再度抬高；Ｒ波丢失和进展性Ｑ波．