建立小鼠急性心肌缺血再灌注损伤模型手术技巧及TTC染色方法探讨

目的探讨建立小鼠缺血再灌注损伤（I/R）模型更好的办法。方法共30只雄性C57BL/6小鼠,其中20只用于建立I/R模型（实验组）,10只为假手术组。采用小动物呼吸机,开胸结扎冠状动脉左前降支（LAD）30 min,待小鼠苏醒后撤离呼吸机。结果行30 min LAD结扎术后实验组存活率为95%（19/20）。实验组和假手术组缺血危险区分别为（59.5±0.9）%、（60.7±1.1）%,P〉0.05;实验组梗死面积为（32.2±0.7）%,假手术组无心肌梗死形成。结论采用本方法制作小鼠心肌I/R模型成功率高,且操作简单,创伤小。     

蛋白酶体抑制剂与心肌再灌注损伤

泛素-蛋白酶体系统是真核细胞内蛋白质代谢的重要途径,参与了细胞周期调节、基因转录和表达、脱氧核糖核酸修复、抗原递呈和炎症过程。现就泛素-蛋白酶体系统与心肌再灌注损伤的关系以及抑制蛋白酶体的活性后对心肌再灌注损伤的影响进行综述。     

胰岛素控制血糖减轻Ⅰ型糖尿病小鼠心肌缺血/再灌注损伤

目的:研究Ⅰ型糖尿病(DM)小鼠心肌缺血/再灌注(I/R)损伤的变化,以及胰岛素(ISL)治疗控制血糖对Ⅰ型DM小鼠心肌I/R损伤的影响.方法:72只健康雄性昆明小鼠以链脲佐菌素(STZ)腹腔注射制备Ⅰ型DM模型,建模后用ISL治疗控制血糖2周.实验分为假手术(sham)组、I/R组、DM+I/R组、DM+ISL+I/...     

心肌缺血再灌注损伤研究进展

正心肌缺血本质是心肌的氧供需求平衡失调,缺血心肌可呈现功能、形态及代谢等方面的损伤[1,2],减少心肌缺血后损伤的最有效办法就是恢复组织灌注。但是,目前遇到的问题是缺血心肌在恢复血液再灌注后,出现了心律失常、心肌能量代谢障碍、心肌细胞超微结构的变化及微血管内皮细胞(VEC)损伤和功能障碍等一系列的功能、结构、代谢及心肌细胞电生理特性等各个方面的损伤进一步加重的现象,即心肌缺血/再灌     

心肌缺血再灌注损伤进展

缺血-再灌注损伤指的是在组织器官缺血恢复血流后,不仅没使组织器官功能恢复,反而使缺血所致的功能和代谢障碍及结构破坏进一步加重,甚至出现不可逆损伤的现象。研究最多的就是心肌缺血-再灌注损伤。随着溶栓、冠状动脉搭桥术、经皮冠状动脉内成形术等血管再灌注疗法通过恢复缺血组织的供血有效挽救濒死心肌。但是再灌注受缺血组织血管再通时间限制并存在再灌注损伤等问题,因此随着新的再灌注技术在临床广泛应用,防治心肌缺血-再灌注损伤成为冠心病治疗亟待解决的关键问题之一。     

亚硝酸盐拮抗心肌缺血再灌注损伤作用的研究进展

近几年的多项研究发现亚硝酸盐可以作为一氧化氮的生理储存池,在缺氧组织,随着氧和pH值的下降而转化为一氧化氮,亚硝酸盐通过抑制线粒体呼吸和限制活性氧的生成,发挥细胞保护作用。大量的动物模型证实了亚硝酸盐对缺血再灌注损伤的细胞保护作用,现通过亚硝酸盐的临床前资料来探讨它对心肌缺血再灌注损伤潜在的治疗作用。     

心肌缺血再灌注损伤的研究进展

对于急性心肌梗死患者,利用溶栓或早期用经皮冠状动脉介入治疗(PCI)进行有效的心肌再灌注是缩小心肌梗死面积,改善临床转归的有效方法.缺血预适应和缺血后适应不仅对动物的心脏有保护作用,同样对人类心脏也具有保护作用.通过再灌注损伤补救激酶(RISK)途径,阻止线粒体转运通道(PTP)开放等干预再灌注损伤递质的措施,能够明显减轻急性心肌梗死患者心肌缺血再灌注损伤.     

白黎芦醇减轻Ⅱ型糖尿病小鼠心肌缺血/再灌注损伤的作用

目的:探讨白黎芦醇(RSV)减轻Ⅱ型糖尿病(T2DM)小鼠心肌缺血/再灌注损伤(MI/RI)的作用及其机制。方法: 采用喂养高脂饮食结合小剂量链脲佐菌素(STZ)建立T2DM小鼠模型。造模成功后立即给予RSV(10mg/kg)每日1次灌胃,连续3周。实验分为正常假手术组、正常手术对照组、DM假手术组、DM手术对照组、RSV组、CpC组,每组20只。手术方式采用心脏冠状动脉左前降支结扎30 min、再灌注3 h或24 h。抑制剂组于术前1 h腹腔注射Compound C（20 mg/kg）。用TTC染色法检测心肌梗死(MI)面积,TUNEL法检测心肌细胞凋亡,ELISA法检测caspase-3活性、血浆脂联素（APN）水平,Western blot法检测AMPK、p-AMPK及脂肪组织APN的含量。结果: 喂养高脂饮食结合小剂量STZ能够成功建立T2DM小鼠模型。与DM手术对照组相比,RSV饲喂能够减轻T2DM小鼠MI/RI,减小MI面积、减少心肌细胞凋亡（P<0.01）,降低caspase-3的活性（P<0.05）。RSV还能够上调脂肪组织APN表达,逆转T2DM小鼠低APN血症（P<0.01）。AMPK抑制剂Compound C可显著减弱RSV的心肌保护作用（P<0.05）。结论: RSV可通过逆转T2DM小鼠的低脂联素血症,在MI/RI时发挥对心肌的保护作用。     

卡维地洛对离体大鼠心肌缺血再灌注损伤的保护作用及机制探讨

目的 研究卡维地洛对离体大鼠心肌缺血再灌注损伤的保护作用,并探讨其可能机制.方法 30只大鼠随机分为空白对照组、缺血再灌组、卡维地洛干预组.采用Langendorff灌注系统,制备离体大鼠缺血再灌注模型,观察各组间大鼠心脏功能及基质金属蛋白酶-9(MMP-9)变化情况.结果 缺血再灌组及卡维地洛干预组较空白对照组MMP-9水平显著增高(P<0.05).卡维地洛干预组较缺血再灌组MMP-9水平显著降低(P<0.05).卡维地洛干预组MMP-9水平与该组大鼠心率变化率呈正相关(r=0.652,P<0.05).结论 卡维地洛可降低缺血再灌注损伤大鼠心肌MMP-9表达水平,其机制可能与β受体阻滞作用有关.     

微小RNA在心肌缺血再灌注损伤中的作用及机制

微小RNA（microRNA,miRNA）是一类在进化上高度保守的小分子非编码RNA,大约南19～25个核苷酸组成,具有转录后渊控蛋白质编码基因表达的功能,     

Tumor-necrosis-factor-alpha-gene-deficient mice have improved cardiac function through reduction of intercellular adhesion molecule-1 in myocardial infarction.

BACKGROUND: Tumor necrosis factor (TNF)-alpha is linked to the pathogenesis of cardiovascular diseases, but how it affects myocardial infarction (MI), so the present study examined the effects of TNF-alpha and the involvement of intercellular adhesion molecule (ICAM)-1 on MI. METHODS AND RESULTS: Left coronary arteries of C57BL/6 wild type (WT) and TNF-alpha knockout (KO) mice were ligated and the mice were killed 1, 3, and 7 days later. Fractional shortening on echocardiography of the KO mice was significantly higher than that of the WT mice from day 1 to 7 (p<0.01). The ICAM-1 mRNA in the infarcted area of the KO mice was significantly lower than that of the WT from day 1 (p<0.01) to 7. In immunohistochemistry, the expression of ICAM-1 was weaker in the KO than in the WT mice. The number of neutrophils in the KO mice peaked at day 1, but even this peak level failed to reach the levels in the infarcted (p<0.01) and peri-infarcted areas (p<0.05) in the WT. The number of macrophages in the KO mice peaked at day 7, but this peak level failed to reach the levels in the infarcted (p<0.01) and peri-infarcted areas (p<0.05) in the WT. CONCLUSION: In a permanent occlusion model of MI TNF-alpha decreased cardiac function and ameliorated myocardial remodeling through the induction of ICAM-1.     

Determinants of improved left ventricular function after thrombolytic therapy in acute myocardial infarction

Many studies have been performed to evaluate the efficacy of thrombolytic therapy in achieving reperfusion, salvaging myocardium and enhancing survival. This review discusses the concordance between the results of these clinical studies and the observations made in experimental animals of the effect of reperfusion on the recovery of left ventricular function. The evaluation of functional recovery is affected by the timing of the measurement and the sensitivity of the method for detecting regional abnormalities. In addition, the underlying coronary anatomy also determines outcome, so that infarct location, collateral circulation and the degree of coronary obstruction merit consideration. Two factors are of paramount importance in determining the amount of myocardium salvaged, the recovery of left ventricular function and the reduction in mortality. These factors are: the time delay until reperfusion is achieved and the adequacy of the coronary reflow. The close agreement between studies measuring the effect of reperfusion on left ventricular function and studies with mortality as the end point provides indirect evidence that enhancement of survival in patients treated with thrombolytic agents is mediated by recovery of ventricular function.     

Haemostatic function in myocardial infarction

Coagulation factor VIII, von Willebrand factor, antithrombin, fibrinogen, plasminogen activator capacity, and inhibitors of fibrinolysis, including a recently discovered fast inhibitor of tissue plasminogen activator, were measured three to six months after myocardial infarction in 116 male and 32 female patients aged less than 45 and in 136 age and sex matched random controls. Plasma concentrations of fibrinogen and the fast inhibitor of tissue plasminogen activator were raised in male patients (with or without correction for orosomucoid levels, blood group distribution, tobacco and alcohol consumption, and weight/height index) and plasminogen activator capacity was reduced. In female patients the concentrations of factor VIII, von Willebrand factor, the fast inhibitor of tissue plasminogen activator, alpha 2-antiplasmin, and C1 inhibitor were significantly increased. The increase in factor VIII concentrations depended strongly on a persisting inflammatory response. Multivariate analysis indicated that a combination of fibrinogen and tissue plasminogen activator inhibitor concentrations gave the best independent discrimination between male patients and controls. For female patients the best combination was von Willebrand factor and tissue plasminogen activator inhibitor. Male patients with multiple vessel atheromatosis at coronary angiography had higher fibrinogen concentrations than those with atheromatosis of a single vessel. Atheromatosis was defined as sharp-edged, plaque-like, or irregular indentations, often multiple, into the vessel lumen without features suggesting fibromuscular hyperplasia.     

CD151对大鼠心肌梗死后血管新生及心功能的影响

目的观察CD151基因对心肌梗死后大鼠梗死心肌微血管密度和心功能的影响,以明确CD151体内促血管新生作用。方法结扎大鼠冠状动脉左前降支建立心肌梗死模型。构建PAAVCD151重组质粒,分点注射至梗死心肌及周围进行基因转染。另外设置心肌内不转染及转染PAAVGFP心肌梗死对照组。4周后测定心肌微血管密度及心功能。结果心肌注射PAAVCD151转染后心肌中CD151蛋白表达明显高于对照组(P<0.01)。转染CD151组心肌微血管密度[(385.4±79.9)N/MM2]明显高于对照组[(240.8±40.3)N/MM2](P<0.01)。心脏收缩功能指标射血分数、短轴缩短率、左室内压最大上升和下降速率等参数亦明显高于对照组(P<0.01)。结论CD151在体内具有明确的促血管生成作用,通过促进缺血心肌的血运重建起到保护心脏功能的作用。