曲尼司特对急性心肌梗死大鼠转化生长因子-β1的影响

目的 探讨曲尼司特对心肌梗死后转化生长因子-β1(TGF-β1)影响的研究.方法 制作急性心肌梗死(AMI)大鼠模型,分为AMI组、曲尼司特组,另取假手术大鼠12只作为对照组.于第4周末处死大鼠,用氯胺T法测定羟脯氧酸含量,用RT-PCR检测大鼠心肌TGF-β1 mRNA(TGF-β1/GAPDH),用免疫印迹法(West-blotting)测定TGF-β1蛋白水平(TGF-β1/β-actin).结果 AMI组大鼠心肌组织TGF-β1mRNA水平、蛋白水平和心肌羟脯氨酸含量均较假手术组明显升高(P<0.01).曲尼司特组大鼠心肌组织TGF-β1 mRNA水平、蛋白水平和心肌羟脯氨酸含量均较心肌梗死组明显降低(P<0.05或P<0.01);但与假手术组比较,各指标均明显升高(P<0.05).结论 曲尼司特能降低大鼠心肌梗死后心肌TGF-β1mRNA和蛋白的表达,这可能是其抑制心肌梗死后心肌纤维化的机制之一.     

曲尼司特对急性心肌梗死大鼠心肌纤维化的影响

目的:观察曲尼司特对大鼠急性心肌梗死(AMI)后心肌纤维化和左室功能的影响。方法:结扎大鼠 冠状动脉制成AMI模型,随机分成假手术组(6只)、AMI组(8只)、曲尼司特组(7只)和苯那普利组(6只)。于 第4周末,用放射免疫法测定血浆和心肌血管紧张素Ⅱ含量,用氯胺T法测定羟脯氨酸含量,动脉插管测定大鼠 左室心功能。结果:与AMI组比较,曲尼司特不能降低血浆和心肌血管紧张素Ⅱ水平,但能减少非梗死区心肌羟 脯氨酸含量,降低左室舒张末压,升高±dp/dt。结论:曲尼司特可减轻AMI后左室心肌纤维化,改善左室功能。     

外源性硫化氢对阿霉素心肌病大鼠心肌纤维化影响的研究

目的:本实验以阿霉素(盐酸多柔比星ADR)诱导的心肌病大鼠为研究对象,探讨外源性硫化氢(H2S)供体硫氢化钠(Na HS)是否通过调控转化生长因子β1(TGF-β1)的表达,从而减轻心肌纤维化。方法:40只,雄性,SD大鼠,随机分为四组:1ADR组(n=12);2 ADR+Na HS组(n=12);3Na HS组(n=8);4对照组(n=8);药物均腹腔注射,连续用药10周,用心脏超声心动仪检测大鼠心功能,用酶联免疫吸附(ELISA)法测定大鼠心肌组织中H2S、TGF-β1以及I型和III型胶原的浓度;用实时荧光定量PCR(RQ-PCR)检测大鼠心肌组织中TGF-β1mRNA的表达量。结果:阿霉素组大鼠心功能较对照组明显降低(P<0.05),心肌组织中TGF-β1以及I型和III型胶原的表达较对照组明显增多(P<0.05),另外H2S浓度较对照组明显减少(P<0.05)。补充外源性硫化氢后大鼠心功能明显好转,心肌组织中TGF-β1以及I型和III型胶原的表达较阿霉素组明显减少(P<0.05)。结论:补充外源性硫化氢可通过减少TGF-β1的表达,减轻心肌纤维化,改善大鼠心功能。     

骨髓基质细胞移植对心肌纤维化的干预

目的:评价骨髓基质细胞移植对心肌梗死后心肌间质纤维化的影响。方法:30只日本大耳白兔,随机分为细胞移植组、药物治疗组、对照组,体外骨髓穿刺提取、分离、培养骨髓基质细胞,心肌梗死模型制作成功2周后沿梗死周边区域注射细胞悬液100μl(细胞移植组)或DMEM培养基100μl(对照组)或给予安体舒通20mg,bid,服用1个月(药物治疗组)。各组实验前、后4周经心脏超声检查,氯胺T氧化法测定血浆、组织羟脯胺酸含量,TTC染色评价梗死面积。结果:细胞移植组血浆、组织羟脯胺酸含量[(22.79±1.69)mg/L、(1.59±0.89)μg/mg]均低于对照组[(40.16±2.31)mg/L、(3.59±0.19)μg/mg]、药物治疗组[(34.24±1.98)mg/L、(2.67±0.81)μg/mg],均P<0.05。实验后4周时,细胞移植组心功能有所提高[LVEF(56.91±2.04)%],与对照组[(32.49±1.29)%]、药物治疗组[(53.22±2.13)%]比较,均P<0.05;梗死面积[(22.82±3.12)%]有所下降,与对照组[(29.73±2.11)%]、药物治疗组[(28.61±1.24)%]比较,均P<0.05。结论:细胞移植后可抑制心肌胶原合成、抑制心肌局部间质纤维化,是细胞移植心功能改善机制之一。     

反复CVB3m感染对小鼠心肌的影响

目的　研究反复病毒感染对小鼠心肌的损伤 ,观察转化生长因子β1(TGF-β1)在反复病毒性心肌损伤心肌基质胶原重建中的作用。方法　通过 3次反复且增量 CVB3 m病毒感染小鼠 ,建立慢性心肌损伤模型 ,于首次感染后第 74d处死小鼠 ,病理、组织化学及电镜分析心肌病理损伤和胶原系统改变 ,计算胶原容积分数。用EL ISA法测定血清 TGF-β1含量。结果　反复病毒感染后小鼠心功能降低 ,心肌胶原容积分数高于对照组 (P <0 .0 5) ,基质胶原明显增生重建 ,主要表现为瘢痕修复和间质纤维化。反复病毒感染组血清 TGF-β1含量 (0 .10 3 5± 1.2 70 0 ) μg/L 高于对照组 (P <0 .0 5)。结论　反复病毒感染对小鼠心肌的影响主要是基质胶原系统的增生重建 ,持续病毒感染和 TGF-β1增高是心肌炎后心室重构及向扩张型心肌病转化的重要原因     

基质金属蛋白酶对大鼠心肌梗死后心室重塑的影响

目的　探讨大鼠心肌梗死后心肌间质基质金属蛋白酶 (MMPs)活性和心室重塑的关系及药物氯沙坦干预的影响。方法　Sprague Dawley(SD)大鼠 82只 ,随机分为对照组 (n =10 )、心肌梗死组 (MI组 ,n =36 )和氯沙坦组 (n =36 )。氯沙坦组予氯沙坦 5 0mg·kg-1·d-1灌胃 ,第 2周开始与MI组予异丙肾上腺素。酶谱法测定各组不同时间MMPs活性 ,氯胺T法测定胶原含量 ,免疫组化法测定I/III胶原比例 ,电镜观察心肌超微结构。结果　心肌梗死组MMP 2、MMP 9活性在各周时间点明显升高 ,胶原含量和I/III胶原比例随后升高。而氯沙坦组MMPs活性、胶原含量和I/III胶原比例较MI组显著降低。结论　大鼠心梗后间质内MMPs活性升高 ,继发胶原含量增加 ,I/III胶原比例升高 ,是心室重塑的重要原因。氯沙坦对MMPs活性的影响可能是其干预心梗后心室重塑的机制之一。     

曲尼司特对糖尿病大鼠肾脏TGF-β1和SGK1表达的影响

目的探讨曲尼司特对糖尿病大鼠肾脏的保护作用及其可能的机制。方法雄性SD大鼠60只,随机均分为4组:正常对照组、模型组、低剂量及高剂量曲尼司特治疗组。后3组均一次性给予链脲佐菌素(STZ)30 mg/kg尾静脉注射建立糖尿病大鼠模型。正常对照组给予等量柠檬酸缓冲液尾静脉注射;模型组不再给药;低、高剂量曲尼司特组于造模后1 w分别给予曲尼司特100 mg·kg-1·d-1和400 mg·kg-1·d-1。造模后8 w处死大鼠,免疫组化检测肾间质组织中的TGF-β1及SGK1表达;Masson染色观察肾间质绿染面积。结果与正常大鼠相比,糖尿病模型大鼠的血糖、尿蛋白定量、肾重/体重、肌酐清除率明显升高(P<0.05);经过曲尼司特处理后,以上指标均有下降,尿蛋白定量、肾重/体重、肌酐清除率下降(P<0.05),且高剂量组与低搅量组相比,尿蛋白定量下降(P<0.05)。Masson染色可见模型组肾间质内大量胶原纤维增生,肾小球局灶性节段性硬化,而曲尼司特组上述改变均有减轻。免疫组化示TGF-β1及SGK1表达趋势一致,正常对照组均低于其他组(P<0.01),曲尼司特组低于模型组,高剂量曲尼斯特组低于低剂量组(P<0.05)。结论曲尼司特能改善糖尿病大鼠的生化指标,下调TGF-β1和SGK1表达,发挥抗纤维化的作用。     

转化生长因子-β1在自发性高血压大鼠肾脏的表达及与肾间质纤维化的关系

目的探讨转化生长因子-β1(TGF-β1)在自发性高血压大鼠(SHR)肾间质的沉积及其与肾间质纤维化的关系和培哚普利高血压肾间质纤维化的治疗作用.方法 SHR大鼠随机分为高血压组和治疗组,WKY大鼠为对照组.ELISA法测血清TGF-β1的浓度;免疫组织化学染色法检测Ⅰ、Ⅲ型胶原和TGF-β1在三组肾间质的沉积;半定量逆转录-聚合酶链反应观察TGF-β1 mRNA在三组肾脏的表达.结果三组血TGF-β1 浓度的差异无显著性(P＞0.05);高血压组肾间质Ⅰ、Ⅲ型胶原及TGF-β1明显增加(P<0.01 or P<0.05),培哚普利能明显减少Ⅰ、Ⅲ型胶原及TGF-β1的沉积,显著降低TGF-β1 mRNA的表达(P<0.01 or P<0.05);Ⅰ、Ⅲ型胶原的表达与肾间质TGF-β1的表达呈正相关(r分别为0.734、0.762,P<0.01),与血清中TGF-β1无关(r分别为0.069、0.180,P＞0.05).结论肾脏局部的TGF-β1参与了自发性高血压大鼠肾间质纤维化.培哚普利可能通过减少局部TGF-β1表达,来减轻肾间质纤维化.     

转化生长因子-β1/TGFβ激活激酶信号表达变化在心房颤动心肌纤维化中的作用

目的 探讨心房颤动的发生过程中是否存在心房肌的纤维化,以及TGF-β1/TAK1信号系统在心房颤动心肌纤维化中的作用.方法 20只新西兰大白兔随机分成两组:假手术组(Group S)和快速起搏组(Group P).给予兔左心房心外膜电起搏,以900次/min高频起搏,建立房颤模型.起搏前后及房颤后记录心电图.取兔心房组织,观察细胞结构变化(HE染色),比较左房重量指数及胶原蛋白的表达水平(Masson染色),免疫组化、Westen-blot检测TGF-β1、TAK1蛋白表达水平,PCR检测TGF-β1mRNA、TAK1mRNA的表达水平.结果 ①起搏兔的左房重量、左房重量指数明显高于Group S.Masson染色显示起搏兔的左心房心肌间质胶原显著增多.②起搏组的TGF-β1、TAK1的表达明显高于Group S.③在起搏组中,代表心肌纤维化的心肌间质胶原及LAWI与TGF-β1、TAK1的表达密切相关(P＜0.05),其中与TGF-β1呈正相关(R2=0.72,P＜0.05),与TAK1亦呈正相关(R2=0.762,P＜0.05).结论 心房颤动在发生早期即存在心房组织的纤维化.快速起搏诱导的心房颤动早期,TGF-β1/TAK1通路信号mRNA及蛋白表达水平明显升高,TGF-β1/TAK1通路信号可能是心房纤维化信号途径之一,可能成为房颤治疗的新靶点.     

早期慢性肾脏疾病心脏病变的实验研究

目的研究早期慢性肾脏疾病大鼠心脏病变情况。方法通过减少肾脏切除量和缩短喂养时间方法建立早期慢性肾脏疾病大鼠动物模型,分析其心脏病变,包括心脏重,体重比值、心肌细胞增大、心肌间质纤维化程度和心肌间质I型、Ⅲ型胶原含量等。结果（1）实验组大鼠血尿素氮水平、尿白蛋白/肌酐比值、肾小球系膜增生程度均高于对照组,但实验组和对照组之间血肌酐水平差异无统计学意义,且病理改变较轻,表明早期CKD模型制作是成功的。（2）实验组大鼠心脏重,体重比值高于对照组（P〈0.01）,心肌细胞肥大,心肌间质纤维化明显。免疫组化测定显示心肌组织内I型和Ⅲ型胶原量均高于对照组（P均〈0.01）。结论心脏病变在早期CKD大鼠动物模型中即已经存在。表现为重量增加、间质纤维化、胶原增多等。     

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.     

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.     

Emergency myocardial revascularization in acute evolving myocardial infarct

Immediate coronary artery bypass for acute evolving myocardial infarction could be the elective therapy if provided on useful time, because myocardial salvage can be achieved by early reperfusion. Thirty eight patients had emergency coronary artery by-pass graft for acute evolving myocardial infarction during the early phase: 35 were male, the mean age was 51 years (34 to 74). The mean interval between the onset of symptoms and surgery in this series of patients was two hours and a half. This interval seems to be also the time limit in our experience to get a partial or complete recovery of ischemic area. Four patients died in hospital, but they were in severe cardiogenic shock before emergency surgery. Twenty nine cases were free of symptoms at a mean follow-up of 18 months (6 to 36) and two suffered for residual angina. Three patients died after discharge few months later: two during redo emergency vein grafts operations, one in deep left ventricular failure, while he was waiting for heart transplant. All these patients operated on as emergency developed acute myocardial infarction during their stay in hospital waiting for catheter study, surgical operation or during percutaneous transluminal coronary angioplasty. Saphenous vein grafts, were used in twenty nine patients, left internal mammary artery in nine cases, single in four and associated to saphenous vein in five, with an average number of anastomoses of 2.6 (1 to 6) for patient. ECG was found to be normal in 76% of the patients operated on within two hours and a half from the beginning of symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)