雷米普利对心肌梗死后心衰大鼠非梗死区胶原的抑制作用

目的 研究心肌梗死后心衰大鼠非梗死区心肌血管紧张素Ⅱ(Ang Ⅱ)及其Ⅰ型受体(AT1-R)表达对心室重构的影响及雷米普利的干预作用.方法 结扎大鼠左冠状动脉前降支并饲养6 w的16只存活大鼠,随机分为模型组及雷米普利组,每组8只,另取8只大鼠为假手术组,连续灌胃给药4 w后测定大鼠血流动力学参数,ELISA方法检测血清及左心室非梗死区AngⅡ的含量,RT-PCR 法测定左心室非梗死区心肌组织AT1-R mRNA表达水平,Masson染色观察非梗死区心肌胶原的沉积.结果 雷米普利能明显升高左心室内压最大上升和最大下降速率(±dp/dt_(max)),降低左心室收缩压(LVSP)、左心室舒张末压(LVEDP)(P<0.05或P<0.01),但对心率(HR)、收缩压(SBP)、舒张压(DBP)无明显影响(P>0.05),同时明显降低血清及左心室非梗死区AngⅡ的含量及下调AT1-R mRNA 表达水平(P<0.01或P<0.001),Masson染色可见非梗死区心肌胶原沉积明显减轻.结论 雷米普利对梗死后心衰大鼠非梗死区心肌间质胶原重构有显著的抑制作用,其作用机制与下调AT1-R表达水平及减轻胶原沉积有关.     

心肌梗死大鼠非梗死区心肌细胞凋亡与间质纤维化的关系

目的探讨心肌梗死后非梗死区心肌细胞凋亡与间质纤维化的关系及其机制。方法雌性Wistar大鼠,通过结扎左冠状动脉前降支制备心肌梗死模型。术后24h、1周、2周及4周随机从各组中各取10~12只大鼠,分别行病理组织学检查及非梗死区心肌组织的胶原容积分数、凋亡细胞、血管紧张素Ⅱ、醛固酮及Ⅰ、Ⅲ型胶原的mRNA检测。结果大鼠梗死范围为24%~33%。术后1~4周心肌梗死组大鼠心肌组织均分布有原位末端标记法染色阳性心肌细胞,且凋亡细胞指数逐渐升高;血管紧张素Ⅱ水平逐渐升高;Ⅲ型胶原mRNA升高。2~4周时心肌梗死组间质亮绿色胶原明显增多,胶原容积分数随着梗死后时间的延长而增加;醛固酮开始升高;Ⅰ型胶原mR-NA明显上升。结论大鼠心肌梗死2周后非梗死区心肌发生细胞凋亡。大鼠心肌梗死2周后非梗死区心肌出现间质纤维化。非梗死区间质纤维化可能与局部肾素—血管紧张素—醛固酮系统激活有关。细胞凋亡可能与间质胶原过度沉积有关。     

芪丹通脉片对心肌梗死后大鼠心肌纤维化重构的影响

目的:观察益气活血复方芪丹通脉片（qidan tongmai tablet,QDTMT）对大鼠心肌梗死(MI)后心功能及左心室非梗死区心肌纤维化的影响。方法: 以结扎SD大鼠左冠脉前降支法建立MI模型,随机分为假手术(Sham)组、MI组、MI+QDTMT小剂量(MI-QDTMTL)组和MI+QDTMT大剂量(MI-QDTMTH)组。术后24 h各组均用生理盐水配制成等体积药液灌胃4周,4周后以多普勒超声评价心脏功能;测定心室的质量/体质量(HW/BW);以MASSON染色检测非梗死区胶原的含量;用RT-PCR法检测非梗死区转化生长因子-β1（TGF-β1）、Ⅰ型胶原蛋白（Collagen type 1,Col1）及Ⅲ型胶原蛋白（Collagen type 3,Col3）mRNA的表达水平。采用大鼠羟脯氨酸（HYP）的ELASA试剂盒检测非梗死区中HYP的含量。结果: ①术后4周心功能:与MI组比较,MI-QDTMTL组和MI-QDTMTH组左室舒张末期内径(LVEDD)和HW/BW均降低,而射血分数(EF)升高（P<0.01或P<0.05）;②非梗死区心肌胶原蛋白的含量: MI-QDTMTL组胶原和MI-QDTMTH组胶原含量均低于MI组（P<0.01）;MI-QDTMTH组胶原的含量明显低于MI-QDTMTL组(P<0.01);③非梗死区TGF-β1、Col1、Col3mRNA的表达:与MI组比较,MI-QDTMTL组、MI-QDTMTH组的TGF-β1 Col1、Col3 mRNA均显著降低(P<0.01或P<0.05);MI-QDTMTH组TGF-β1、Col1、Col3 mRNA的表达显著低于MI-QDTMTL组(P<0.05);④非梗死区HYP的含量: MI-QDTMTL组与MI-QDTMTH组HYP的含量低于MI组(P<0.05,P<0.01); MI-QDTMTH组HYP的含量低于MI-QDTMTL组(P<0.05)。结论: QDTMT通过下调MI交界区TGF-β1、Col1、Col3 mRNA的表达及HYP产生,进而抑制MI后非梗死区反应性胶原的过度沉积,且高剂量组比低剂量组的疗效更好,为防治MI后非梗死区心肌纤维化重构,改善心脏功能提供了新的治疗思路。     

依那普利和氯沙坦对心肌梗死大鼠心室重构影响的比较

目的 研究比较血管紧张素转换酶抑制剂(ACEI)及选择性血管紧张素Ⅱ受体拮抗剂(AT_1受体拮抗剂)对心肌梗死大鼠心室重构的影响.方法Wistar大鼠冠脉结扎制成心肌梗死模型,24小时后随机分为依那普利(enalapril)治疗组,氯沙坦(losartan)治疗组,安慰剂(placebo)组,治疗6周.假手术组为对照.6周后测定体重、梗死区重量、心脏重量/体重、血浆及心肌的血管紧张素Ⅱ(AngⅡ)浓度、心肌胶原含量及血浆内皮素浓度.结果enalapril及losartan治疗组中心脏重量/体重及心脏胶原含量高于假手术组,而低于安慰剂组.在三个梗死组中,梗死区的重量无显著差异.enalapril治疗组血浆AngⅡ浓度降低,而losartan治疗组中血浆AngⅡ浓度升高.梗死后安慰剂组心脏局部AnsⅡ浓度明显高于假手术组、enalanril和losartan治疗组.enalanril及losartan可降低血浆ET-1浓度.结论血管紧张素转换酶抑制剂及血管紧张素Ⅱ受体拮抗剂对阻止心室重构的发展具有相同作用.     

心肌梗死大鼠非梗死区间质纤维化及机制探讨

目的:探讨心肌梗死后不同阶段非梗死区心肌胶原的变化及其发生机制。方法:雌性Wistar大鼠,通过结扎左冠状动脉前降支制备心肌梗死模型。分为心肌梗死组(最终存活32只)和假手术组(最终存活47只),于术后24h、1周、2周及4周随机从两组中各取10~12只大鼠,分别行病理组织学、心肌胶原容积密度分数(CVF)、肿瘤坏死因子-α(TNF-α)、基质金属蛋白酶-9(MMP-9)、血管紧张素Ⅱ(AngⅡ)和醛固酮(ALd)水平的分析,以及Ⅰ型胶原(col-1)及Ⅲ型胶原(col-3)的信使核糖核酸(mRNA)检测。结果:大鼠梗死范围为24%~33%。心肌组织Messon染色显示,假手术组间质只可见散在亮绿色胶原;术后24h~1周,心肌梗死组间质亮绿色胶原与假手术组基本相似;术后2~4周最明显。肿瘤坏死因子-α的表达在梗死后1~4周显著增强。心肌血管紧张素Ⅱ水平术后1~4周,心肌梗死组均高于假手术组,有显著性差异(P<0.05~0.001)。心肌醛固酮含量术后2~4周,心肌梗死组也明显于高假手术组,有显著性差异(P<0.05~0.001)。Ⅰ型胶原mRNA水平术后2~4周心肌梗死组明显高于假手术组;Ⅲ型胶原mRNA水平术后1~4周心肌梗死组明显高于假手术组(P均<0.05)。基质金属蛋白酶-9表达无变化。结论:①大鼠心肌梗死2周后非梗死区出现明显间质纤维化。②非梗死区间质纤维化可能与局部肾素血管紧张素醛固酮系统激活后增加血管紧张素Ⅱ水平及肿瘤坏死因子-α上调有关。③大鼠心肌梗死后4周内非梗死区基质金属蛋白酶-9表达无明显变化。     

药物干预对大鼠急性心肌梗死组织肾素-血管紧张素系统的影响

目的 :观察氯沙坦、培多普利对大鼠急性心肌梗死 (AMI)后组织肾素 血管紧张素系统 (RAS)的影响。方法 :结扎左冠状动脉制作AMI模型 ,随机分为对照组 (C组 ) ,氯沙坦组 (L组 ) ,培多普利组 (P组 ) ,氯沙坦加培多普利组 (LP组 ) ,假手术组 (S组 )。 3d、1和 6周后观察心脏组织血管紧张素Ⅱ (AngⅡ )、血管紧张素转化酶 (ACE)、左心室梗死区和非梗死区AngⅡ 1型受体 (AT1R)和AT2 RmRNA表达的变化。结果 :①C组和L组非梗死区心肌组织AngⅡ含量均显著高于S组 (均P <0 .0 1) ,P组和LP组非梗死区心肌组织AngⅡ含量和ACE水平均显著低于C组和L组 (P <0 .0 1)。②AT1RmRNA表达率 :术后 3d ,4个MI组梗死区均明显增高 (P <0 .0 1) ,1周时 ,非梗死区C和P组显著高于S组 (均 P <0 .0 1) ,梗死区C和P组 (P<0 .0 1)及L和LP组 (P<0 .0 1)显著增高。 6周时 ,非梗死区和梗死区C和P组显著增高 (P <0 .0 1)。③AT2 RmRNA表达率 :3d时 ,梗死区 4个MI组显著增高 (P <0 .0 5 ) ;1周和 6周 ,4个MI组非梗死区 (C组和P组 :P <0 .0 5 ;L组和LP组 :P<0 .0 1)和梗死区 (P <0 .0 1)均显著增高 ;1周时L组梗死区和非梗死区显著高于C组和P组 (P <0 .0 5 ) ;6周时L组和P组在梗死区和非梗死区显著高于C组和P组 (P <0 .0 5 )。结论 :氯沙坦、培     

芦沙坦和西拉普利对大鼠心肌梗死后心肌间质胶原重构的影响

目的　研究芦沙坦和西拉普利对心肌梗死 (MI)后梗死区 (IZ)和非梗死区 (NIZ)胶原沉积的影响。方法　大鼠MI后第 2天用芦沙坦 ,或西拉普利治疗 6周或不治疗 ,并设假手术组。结果　与假手术组比 ,MI组左心室最大上升速率 (+P’max)和下降速率 (-P’max)明显降低 ,而左心室舒张末压 (LVEDP)、血浆Ⅲ型前胶原氨基末端肽 (PⅢNP)和Ⅰ型前胶原羧基末端肽 (PⅠCP)、IZ和NIZ胶原含量和胶原Ⅰ Ⅲ比值均明显增加。与MI组比 ,芦沙坦和西拉普利治疗组 +P’max和 -P’max增加 ,PⅢNP和PⅠCP含量下降。西拉普利使NIZ胶原含量和胶原Ⅰ Ⅲ比值明显降低并轻度降低IZ胶原含量。芦沙坦对胶原含量无明显影响。结论　在大鼠MI后早期应用西拉普利和芦沙坦治疗都能改善血流动力学 ,但抑制心肌纤维化的作用芦沙坦不如西拉普利明显     

合用卡托普利和氯沙坦对大鼠急性心肌梗死后梗死区胶原修复及早期左心室重构的影响

目的探讨大鼠急性心肌梗死(AMI)后早期联用血管紧张素转化酶抑制剂(ACEI)和血管紧张素受体拮抗剂(ARB)对梗死区生长因子及胶原浓度的影响以及继而对左心室重构的影响。方法AMI大鼠随机分成对照组、卡托普利组和合用组,用药14d后测定梗死区及非梗死区血管紧张素Ⅱ(AngⅡ)、转化生长因子-β1(TGF-β1)及羟脯氨酸含量、心功能、左心室容积及重量。结果合用组梗死区AngⅡ、羟脯氨酸含量低于卡托普利组,TGF-β1也有减低趋势,而非梗死区AngⅡ、TGF-β1及羟脯氨酸含量2组间无差异。用药组对心脏功能的影响差异无显著性,合用组左心室舒张功能有低于卡托普利组的趋势;合用组左心室重量大于卡托普利组,但2组左心室容积差异无显著性。结论AMI后早期联用ACEI和ARB降低梗死区生长因子及胶原含量,不利于梗死区修复和左心室的较早期重构。     

磷酸肌酸钠对血管紧张素Ⅱ诱导的乳鼠心肌成纤维细胞增殖和胶原合成的影响及机制研究

目的：观察磷酸肌酸钠对血管紧张素Ⅱ（AngⅡ）诱导的乳鼠心肌成纤维细胞(CF)增殖和胶原合成的影响,并初步探索磷酸肌酸钠抗心肌纤维化的作用机制。
　　方法：将20只Wistar乳鼠取出心脏,体外原代、传代培养CF。实验分4组（每组n=3）,对照组：无血清的DMEM培养液培养CF;AngⅡ组：含AngⅡ1×10-6mol/L的无血清DMEM培养液;磷酸肌酸钠组：含磷酸肌酸钠10 mmol/L的无血清DMEM培养液;AngⅡ+磷酸肌酸钠组：含磷酸肌酸钠10 mmol/L 加AngⅡ1×10-6mol/L的无血清DMEM培养液。采用流式细胞术测定细胞周期分布,Van Gieson（VG）氏染色法测定胶原含量,免疫细胞化学法检测磷酸化细胞外信号调节激酶（pERK1/2）蛋白的表达水平。
　　结果：与对照组相比,AngⅡ组CF的S期细胞百分率明显增加,G0/G1期、G2/M期细胞百分率降低,胶原含量增加, pERK1/2蛋白表达增高,差异均有统计学意义（P均<0.01)。与对照组比较,磷酸肌酸钠组CF细胞周期、胶原含量和pERK1/2蛋白表达,差异均无统计学意义（P均>0.05)。与对照组比较,AngⅡ+磷酸肌酸钠组pERK1/2蛋白表达升高,差异有统计学意义（P<0.01),CF细胞周期和胶原含量差异均无统计学意义（P均>0.05)。与AngⅡ组比较,AngⅡ+磷酸肌酸钠组G0/G1期、G2/M期细胞百分率升高,S期百分率降低,胶原含量减少,pERK1/2蛋白表达降低,差异均有统计学意义（P均<0.01)。
　　结论：磷酸肌酸钠可部分抑制AngⅡ诱导的CF增殖和胶原合成增加,其机制可能与抑制ERK1/2过度激活有关。这提示磷酸肌酸钠可以明显改善AngⅡ诱导的心肌纤维化。     

西洋参叶20s-原人参二醇组皂苷对大鼠实验性心室重构的影响

目的 研究西洋参叶20s-原人参二醇组皂苷(PQDS)对大鼠急性心肌梗死晚期缺血再灌注后心室重构的影响及机制.方法 大鼠结扎左冠状动脉前降支2 h后,松扎再灌注28 d制备急性心肌梗死晚期缺血再灌注后心室重构模型,同时应用PQDS治疗,给药28 d后测定心室重构大鼠心脏形态学参数,血浆血管紧张素Ⅱ(ATⅡ)及内皮素(ET)水平.结果 与心室重构模型组比较,PQDS 50、100 mg·kg~(-1)·d~(-1)均能显著降低非梗死区室间隔厚度及左室腔面积/左室总面积比值(P<0.05及P<0.01),减少梗死区胶原沉积(P<0.05),降低非梗死区Ⅰ型及Ⅲ型胶原蛋白比值(P<0.05),并显著降低血浆ATⅡ及ET水平(P<0.05及P<0.01).两组间各项指标无显著差异. 结论 PQDS能够抑制大鼠实验性心肌梗死晚期缺血再灌注后的心室重构,其机制可能与降低血浆ATⅡ及ET水平,改善胶原重构相关.     

Anaerobic myocardial abscess following myocardial infarction

An anaerobic myocardial abscess due to Bacteroides fragilis developed in a 60-year-old man when he had an acute myocardial infarction while recuperating from surgery for a paracolonic abscess. Anaerobic bacteremia is a common event and may lead to infection in areas of low oxygen tension far removed from the original portal of entry.     

曲尼司特对心肌梗死后心肌间质纤维化的影响

目的探讨曲尼司特对兔心肌梗死后心肌间质纤维化干预作用。方法结扎左前降支制作兔心肌梗死模型,分实验组和对照组。3周后经胃管分别给予曲尼司特及安慰剂1月,心脏彩超评价心功能并检测血清转化生长因子（transform ing growth factor,TGF-β1）,I、III型胶原浓度及组织羟脯胺酸含量。结果实验组治疗前后心功能、心腔内径、室壁厚度明显改善,血清TGF-β1,I、III型胶原浓度及羟脯胺酸含量较对照组明显下降。结论曲尼司特可有效拮抗心肌梗死后心肌间质纤维化,预防心室重构。     

Transient myocardial ischaemia after acute myocardial infarction

The prevalence and characteristics of transient myocardial ischaemia were studied in 203 patients with recent acute myocardial infarction by both early (6.4 days) and late (38 days) ambulatory monitoring of the ST segment. Transient ST segment depression was much commoner during late (32% patients) than early (14%) monitoring. Most transient ischaemia (greater than 85% episodes) was silent and 80% of patients had only silent episodes. During late monitoring painful ST depression was accompanied by greater ST depression and tended to occur at a higher heart rate. Late transient ischaemia showed a diurnal distribution, occurred at a higher initial heart rate, and was more often accompanied by a further increase in heart rate than early ischaemia. Thus in the first 2 months after myocardial infarction transient ischaemia became increasingly common and more closely associated with increased myocardial oxygen demand. Because transient ischaemic episodes during early and late ambulatory monitoring have dissimilar characteristics they may also have different pathophysiologies and prognostic implications.     

Assessment of myocardial viability using myocardial contrast echocardiography

Myocardial contrast echocardiography (MCE) is a technique that uses microbubbles as a tracer during simultaneous ultrasound of the heart. The microbubbles can be used to provide quantitative information regarding the adequacy of myocardial blood flow (MBF), as well as the spatial extent of microvascular integrity. In acute myocardial infarction, MCE can identify the presence of collateral flow within the risk area, and can therefore predict preservation of myocardial viability and ultimate infarct size even prior to reperfusion. After reperfusion, the extent of microvascular no-reflow can be determined, and has significant implications for recovery of left ventricular function. In chronic ischemic heart disease, MCE has also been shown to successfully differentiate viable from necrotic myocardium. This technique can accurately predict recovery of function after revascularization. More importantly, MCE can be used to identify viable segments that may help to prevent infarct expansion and remodeling, and thus improve patient outcomes.     

Assessment of myocardial viability with myocardial contrast echocardiography

The application of noninvasive imaging techniques to assess myocardial viability has become an important part of routine management of patients with acute myocardial infarction and chronic coronary artery disease. Information regarding the presence and extent of viability may help identify patients likely to benefit from revascularization or therapy directed at attenuating left ventricular remodeling. Myocardial contrast echocardiography (MCE) is capable of defining the presence and extent of viability by providing an accurate assessment of microvascular integrity needed to maintain myocellular viability. It is especially suited for the spatial assessment of perfusion, even when myocardial blood flow is reduced substantially in the presence of severe epicardial stenoses or in a bed dependent on collateral perfusion. The routine use of MCE to evaluate viability in patients with acute and chronic coronary artery disease is now feasible with the advent of new imaging technologies and microbubble agents capable of myocardial opacification from venous injections. The utility of this technique for determining treatment strategies has not been established but is forthcoming.     

经静脉心肌声学造影评价心肌梗死后存活心肌的价值

目的　探讨经静脉心肌声学造影 (MCE)对心肌梗死后存活心肌的诊断价值。方法　 2 4例心肌梗死患者用二维超声评价室壁运动情况 ,同时经静脉进行MCE ,以 3个月后静态超声心动图左室心肌节段性运动改善为依据评价MCE对心肌梗死后存活心肌的诊断价值。结果　在 2 4例病人的 384个心肌节段中 ,运动异常节段 184个。在运动异常的 184个节段中 ,MCE1分 39段 ,0 5分 5 0段 ,0分 95段。 3个月复查 79个节段有运动改善 ,其中 39段来自MCE1分的心肌 ,4 0段来自MCE0 5分的心肌。MCE对预测心肌梗死后室壁运动改善的敏感性、特异性、阳性预测值、阴性预测值及准确率分别为 :10 0 %、89 7%、84 8%、10 0 %和 94 6 %。结论　MCE能比较准确地预测心肌梗死后心肌的存活性     

Transient myocardial ischaemia after acute myocardial infarction.

The prevalence and characteristics of transient myocardial ischaemia were studied in 203 patients with recent acute myocardial infarction by both early (6.4 days) and late (38 days) ambulatory monitoring of the ST segment. Transient ST segment depression was much commoner during late (32% patients) than early (14%) monitoring. Most transient ischaemia (greater than 85% episodes) was silent and 80% of patients had only silent episodes. During late monitoring painful ST depression was accompanied by greater ST depression and tended to occur at a higher heart rate. Late transient ischaemia showed a diurnal distribution, occurred at a higher initial heart rate, and was more often accompanied by a further increase in heart rate than early ischaemia. Thus in the first 2 months after myocardial infarction transient ischaemia became increasingly common and more closely associated with increased myocardial oxygen demand. Because transient ischaemic episodes during early and late ambulatory monitoring have dissimilar characteristics they may also have different pathophysiologies and prognostic implications.