基质金属蛋白酶在动脉粥样斑块病变中的作用

动脉粥样硬化是由基因遗传因素（先天性因素）和环境因素（继发性因素）共同作用,互相促进．导致动脉粥样硬化发生、发展。基质金属蛋白酶（matrix metalloproteinases, MMPs）是降解细胞外基质（extraeellular matrix,ECM）最重要的酶类,可降解细胞外基质．与冠脉综合征、急性心肌梗塞等疾病的发生、发展密切相关。     

动脉粥样硬化中基质金属蛋白酶的研究进展

动脉粥样硬化是引起冠状动脉粥样硬化性心脏病的众多因素中最重要的一种,严重威胁到人类的健康和生命。研究发现基质金属蛋白酶在动脉粥样硬化的发生、发展中起重要作用。本文章主要通过叙述基质金属蛋白酶定义,来源、结构和分类等生物学基本特点及基质金属蛋白酶在血管重构和动脉粥样硬化斑块不稳定性中的作用,来阐述基质金属蛋白酶在动脉粥样硬化中的研究进展。     

基质金属蛋白酶在心室重构及充血性心力衰竭中的地位

心室重构是决定心脏病患者心功能及其预后的主要因素之一。心室重构往往伴随着心肌细胞外基质(ECM)的改变,而心肌细胞外基质由结构蛋白和一些生物活性物质组成。在心肌中存在能特异降解细胞外基质基质成分的基质金属蛋白酶(matrix metalloprteinase,MMP),是重构过程中基质     

辛伐他汀对心衰大鼠心功能及基质金属蛋白酶的影响

目的探讨辛伐他汀对心衰大鼠心功能及基质金属蛋白酶的影响。方法35只雄性Wistar大鼠用腹主动脉缩窄法制作慢性心衰模型,分为假手术组(SH组)10只,心衰组(CHF组)12只,辛伐他汀组(CHF-S组)11只,CHF-S组应用辛伐他汀干预。4周后检测三组大鼠血流动力学指标及心肌中基质金属蛋白酶9(MMP-9),基质金属蛋白酶抑制物1(TIMP-1)含量的变化。结果CHF组与SH组相比,血流动力学指标有明显差异(P<0.05),心肌中MMP-9明显升高(P<0.05),TIMP-1明显降低(P<0.05),CHF-S组上述指标改善。结论辛伐他汀能够改善心衰大鼠心功能与心室重构,其机制可能与改变MMPs与TIMPs的平衡失调有关。     

基质金属蛋白酶在青光眼中的研究进展

细胞外质基(extracellular matrix，ECM)是存在于细胞之间的动态网状结构，主要有胶原、糖蛋白、葡萄糖氨基糖苷及蛋白聚糖四大类构成。ECM在维持正常组织功能和结构以及细胞生长、分化、增殖等生理过程和肺瘤的侵袭与转移、血管形成等病理过程中起重要作用。基质金属蛋白酶(matrix metalloproteinase，MMP)系统在ECM合成和降     

基质金属蛋白酶及其组织抑制物与心血管疾病的关系

基质金属蛋白酶(Matrix Metalloproteinases,MMPs)是一组能特异性降解细胞外基质(ECM)及构成成份的锌离子(Zn2+)依赖性蛋白水解酶家族,金属蛋白酶组织抑制因子(Tissue Matrix Metalloprote Inaseinhibitors,TIMPs)是MMPs的特异性内源性抑制酶,MMPs和TIMPs之间的动态平衡是维     

基质金属蛋白酶在妇产科领域的研究进展

<正>基质金属蛋白酶(matrix metalloproteinases,MMPs)是由Gross和Lepiere[1]1962年研究蝌蚪时首次发现,1992年Woessner[2]首次完整地介绍了MMPs及基质金属蛋白酶组织抑制物(TIMPs)的生物学特性。MMPs是一组锌、钙依赖的蛋白水解酶,主要作用是水解细胞外基质,其活性可被TIMPs抑制。目前已发现的MMPs有30余种。近年来发现MMPs与妇产科领域中许多疾病关系密切,如宫颈癌、子宫内膜癌、卵巢癌、子宫内膜异位症及妊娠相关疾病如自然流产、早产、胎膜早破、妊娠期高血压疾病、胎儿生长受限、葡萄胎等,并有了大量的研究。现综述如下。     

基质金属蛋白酶的研究进展

基质金属蛋白酶（matrix metalloproteinases，MMPs）是一类生物活性依赖于锌离子、有降解细胞外基质（extracellar matrix，ECM）能力的内肽酶家族。迄今为止，人类中已识别和定性的有23种。MMPs广泛参与心血管重构、关节炎、风湿活动、纤维化及肿瘤转移等生理及病理过程，涉及机体多个系统。根据作用底物的特异性，MMPs家族可分为胶原酶（MMP-1，8，13，18）、明胶酶（MMP-2，9）、基质酶（MMP-3，10，11）、膜型MMPs（MMP-14，15，16，即MT1，2，3-MMP）和其他型（MMP-7，12，19，20，26）髓。MMPs的组织型抑制剂（tissue inhibitors of metalloproteinases，TIMPs）通过与其高度保守的锌结合位点共价结合而特异性抑制MMPs的活性，共同调节基质代谢。笔者现将其在心血管领域的研究进展作一综述。     

基质金属蛋白酶抑制剂的研究进展

基质金属蛋白酶(MMPs)是一类钙离子和锌离子依赖的内肽酶,它们介导细胞外基质(ECM)的降解和组织重塑,促进肿瘤的侵袭和转移,调节宿主防御反应及正常的细胞功能。MMP抑制剂(MMPIs)可用于治疗肿瘤、骨关节炎及类风湿关节炎等疾病。近来发展了许多不同类别的抑制剂,但都未通过临床试验,故需采用不同的锌离子结合基(ZBG)设计具有选择性的抑制剂。本文概括了MMPs的三维结构,MMPIs的现状,小分子质量MMPIs的设计。综述了各类抑制剂的结构特点、治疗用途及已进入人类临床试验的化合物。     

Icariin attenuates cardiac remodelling through down-regulating myocardial apoptosis and matrix metalloproteinase activity in rats with congestive heart failure

Objectives In this study, the anti‐heart failure effect of icariin, a natural flavonol glycoside, and the underlying mechanisms were investigated. Methods Heart failure was induced by isoproterenol in male Sprague–Dawley rats. Matrix metalloproteinase activity was determined by gelatin zymography assay. The mRNA expression was determined by real‐time PCR. The protein expression was determined by Western bolt. Mitochondria structure was examined by transmission electron microscopy. Key findings Isoproterenol administration resulted in a severe heart failure, as shown by the increased levels of left ventricular weight index, heart rate, left ventricular end diastolic pressure, maximal rate of left ventricular pressure decline (dp/dt_min), decreased levels of left ventricular systolic pressure and maximal rate of left ventricular pressure rise (dp/dt_max). Against these, icariin dose‐dependently reversed the changes of these cardiac morphometric and haemodynamic parameters. In addition, icariin significantly inhibited serum levels of tumour necrosis factor‐α, noradrenaline, angiotensin II and brain natriuretic peptide in rats with congestive hear failure and improved the histological changes, including cardiocyte hypertrophy, cardiocyte degeneration, inflammatory infiltration and cardiac desmoplasia. Furthermore, the expression and activity of matrix metalloproteinase (MMP)‐2 and MMP‐9, which regulate collagen production, were also blocked by icariin. Moreover, myocardial apoptosis was remarkably attenuated by icariin through regulating Bcl‐2/Bax axle. Conclusions Icariin ameliorates left ventricular dysfunction and cardiac remodelling through down‐regulating matrix metalloproteinase‐2 and 9 activity and myocardial apoptosis in rats with congestive heart failure.     

Targeting matrix metalloproteinases in heart disease: Lessons from endogenous inhibitors

Basic pharmacological/transgenic studies have clearly demonstrated a cause–effect relationship between the induction and activation of matrix metalloproteinases (MMPs) and adverse changes in the structure and function of the left ventricle (LV). Thus, regulation of MMP induction and/or activation would appear to be a potential therapeutic target in the context of cardiovascular disease, such as following myocardial infarction (MI). However, pharmacological approaches to inhibit MMPs have yet to be realized for clinical applications. The endogenous inhibitors of the MMPs (TIMPs) constitute a set of 4 small molecules with unique functionality and specificity. Thus, improved understanding on the function and roles of individual TIMPs may provide important insight into the design and targets for pharmacological applications in LV remodeling processes, such as MI. Therefore, the purpose of this review will be to briefly examine biological functions and relevance of the individual TIMPs in terms of adverse LV remodeling post-MI. Second is to examine the past outcomes and issues surrounding clinical trials targeting MMPs in the post MI context and how new insights into TIMP biology may provide new pharmacological targets. This review will put forward the case that initial pharmacological attempts at MMP inhibition were over-simplistic and that future strategies must recognize the diversity of this matrix proteolytic system and that lessons from TIMP biology may lead to future therapeutic strategies.     

心衰治疗靶点与干预研究进展

随着对心衰发病、进程以及恶化病理生理过程了解的不断深入,心衰新靶点的干预正在成为治疗心衰的希望。文中综述了心肌肥厚过程中包括钙调神经磷酸酶(CaN)、G蛋白、糖原合酶激酶3(GSK3)、肌细胞增强因子2(MEF2)、过氧化物酶体增生激活受体(PPAR)、小G蛋白(smallG protein)、Na+/H+交换体(NHE)、亚细胞器(subcellular organelles)的治疗靶点,以及天冬氨酸特异性半胱氨酸蛋白酶(Caspase)、核酸内切酶、凋亡调节因子等细胞凋亡治疗靶点与干预,同时,也综述了内皮素及受体、炎性因子及贫血治疗新靶点的干预药物、干预措施及机制,为心衰治疗、新药研发提供思路。     

Profound spontaneous hypoglycemia in congestive heart failure

Summary

Eleven cases of spontaneous hypoglycaemia in congestive heart failure in adults are reported. There were 5 males and 6 females, aged from 15 to 65 years (mean, 44 years). Blood sugar ranged from 2 to 42?mg/100 ml (mean 21?mg/100 ml). Six patients were in coma on admittance, 1 was confused, and 4 were conscious. The underlying condition was rheumatic valvular heart disease (3), chronic obstructive lung disease (4), coronary heart disease (3) and cardiomyopathy (1). Five of the 11 patients died. The mechanism of hypoglycaemia is discussed and thought to be a combination of factors such as liver dysfunction, low calorie intake, malabsorption, and increased glucose utilization by ischaemic tissues, including the heart. It is recommended that in patients with congestive heart failure presenting with coma or confusion, blood sugar should be checked for possible hypoglycaemia.     

左旋多巴治疗充血性心力衰竭

左旋多巴０．２５－０．７５ｇ，ｐｏ，ｔｉｄ治疗４２例（男性２５例，女性１７例，年龄５４±ｓ１３ａ）充血性心力衰竭病人，４ｗｋ为一个疗程。结果，临床显效率为６２％，总有效率为９０％。二维超声心动图测定心功能（ＣＯ、Ｃｌ、ＥＦ）改善，心脏Ｘ线正位片心胸比率缩小，与治疗前比较均有显著性差异（Ｐ＜０．０５），不良反应小。     

Bumetanide in congestive heart failure

Summary

Bumetanide, a new diuretic exerting its major effect on the ascending limb of the loop of Henle, was evaluated in 20 patients with congestive heart failure. Dosage ranged from 1 mg to 3 mg daily depending on the patient's condition. The results after 3 and 8 days' treatment showed that bumetanide caused a significant diuresis, an increased excretion of sodium, potassium and chloride, and a comparable fall in the serum levels of these electrolytes. Changes in electrolyte levels were directly related to the dose of the drug. The resultant hypochloraemia was accompanied by a slight metabolic alkalosis.

A comparative crossover study between placebo, bumetanide and frusemide using equipotent doses was performed in 10 patients. Both drugs had a similar effect upon water excretion and the serum and urinary electrolytes.     

低剂量螺内酯治疗充血性心力衰竭临床疗效观察

目的观察低剂量螺内酯治疗充血性心力衰竭(CHF)的临床疗效.方法100例CHF患者随机分成螺内酯组52例,对照组48例,螺内酯组在常规治疗的基础上加用螺内酯20～40 mg/d,连续应用8周以上.结果螺内酯组与对照组比较左室射血分数、每搏输出量和临床疗效差异有显著性(P＜0.05).结论螺内酯治疗充血性心力衰竭有较好的临床疗效,可改善心功能和临床症状,降低病死率.     

非洛地平治疗肺心病心力衰竭

目的：观察常规疗法加非洛地平治疗肺心病心力衰竭的疗效和安全性。方法：肺心病心力衰竭病人 ５０例（男性 ４０例,女性 １０例;年龄 ６８ａ± ｓ8ａ）,在常规治疗基础上,加用非洛地平５mg,po,ｑｄ,连用 ７ ｄ。另有常规治疗组 ５０例（男性 ３８例,女性 １２例;年龄 ６５ ａ± ７ ａ）,仅用吸氧、抗感染、改善通气等常规处理。结果：治疗７ｄ后非洛地平组总有效率 ９８％与常规治疗对照组 ４６％比较,差别有非常显著意义（ Ｐ＜ ０． ０１）, ２组均未发现严重不良反应。结论：非洛地平治疗肺心病心力衰竭疗效优于常规治疗组。     

β受体阻滞剂在心力衰竭治疗中的应用

目的 介绍β受体阻滞剂治疗充血性心力衰竭(CHF)的病理生理、作用机制、应用指征和注意事项。方法 通过查阅国内外相关文献，综述对CHF的治疗应干预神经内分泌、减轻儿茶酚胺类对心肌的直接损害，从而明确β受体阻滞剂对CHF的治疗作用。结果 在标准化治疗的基础上合理使用β受体阻滞剂对Ⅱ～Ⅲ级(按NYHA分级)心力衰竭病人疗效确切。结论 稳定的轻、中度心力衰竭，NHYA分级Ⅱ～Ⅳ级病人，标准治疗加用β受体阻滞剂，可明显改善病人预后及降低死亡率，提高生活质量。     

老年充血性心力衰竭患者血清甲状腺激素的变化

目的：观察老年人充血性心力衰竭（CHF）患者血清甲状腺激素（TH）的改变,探讨TH与CHF病情和预后的关系。方法：观察组（60例）按NYNA心功能分级标准分类心力衰竭等级,用放射免疫法血清游离三碘甲状腺原氨酸（FT3）、游离甲状腺素（FT4）、促甲状腺素（TSH）各参数水平,并与对照组（30例）比较。结果：与对照组比较,FT3明显降低（P＜0．01）,FT4降低仅见于部分心功能Ⅳ级患者,而TSH无显著改变;心衰愈重FT3降低愈明显,两者呈正相关。结论：老年人CHF患者存在继发性TH代谢异常,FT3和（或）FT4降低可作为CHF患者病情和预后判断的指标。