蛇毒中的降压组分—血管紧张素转化酶抑制剂

蛇毒中的一些多肽能够竞争性的抑制血管紧张素转化酶,起到降血压的作用,这些多肽波称为血管紧张素转化酶抑制剂(Angiotensin ConvertingEnzyme Iinhibitor——ACEI)。有关 ACEI 的研究和应用,是近年来心血管药物的一大进展,它可用于抗充血性心     

血管紧张素转换酶基因多态性与2型糖尿病发病的相关性研究

目的:探讨血管紧张素转换酶基因(ACE)多态性与其血清水平及2型糖尿病(T2D)发生的相关性.方法:应用聚合酶链反应检测T2D患者287例和正常对照组307例健康人的ACE基因Alu重复序列的插入/缺失(I/D)多态性,采用全自动生化分析仪检测ACE活性及血脂水平,采用SPSS11.0软件包统计分析基因型分布和等位基因频率与其活性、血脂水平及T2D的相关性.结果:ACE I/D多态性在T2D组(DD:13.36%、ID:45.93%、Ⅱ:40.72%)与对照组(DD:13.24%、ID:43.90%、Ⅱ:42.86%)的基因频率无显著性差异(P0.05).T2D组ACE各基因型之间ACE活性有显著性差异(P<0.01).T2D各基因型的血脂水平分析显示Ⅱ型与DD型之间HDL有显著性差异(P<0.05).结论:ACE基因DD型和D等位基因与ACE活性显著相关,但ACE I/D多态性不是T2DM发生的危险因素且无关,DD型与高HDL水平相关.     

内蒙古地区达斡尔族血管紧张素转换酶基因多态性分布

目的:研究内蒙古地区达斡尔族血管紧张素转换酶基因(ACE)多态性分布。方法:采用聚合酶链反应检测198例北方汉族和198例达斡尔族中血管紧张素转换酶基因插入/缺失(I/D)多态性分布。结果:ACE基因多态性,达斡尔族人群ID、DD基因频率高于北方汉族,II基因频率低于北方汉族,二组间比较均存在明显差异(P<0.05)。结论:北方汉族与达斡尔族间ACE基因多态性和等位基因频率分布存在差异。     

血管紧张素转换酶2-血管紧张素1-7-Mas轴对血管作用的研究进展

血管紧张素转换酶2（ACE2）和Mas受体的发现使人们对肾素-血管紧张素（RAS）有了更全面的认识。ACE2可水解血管紧张素Ⅰ和血管紧张素Ⅱ直接或间接生成血管紧张素1-7（Ang 1-7）,并与高血压的形成密切相关。Ang 1-7主要通过Mas受体引起血管舒张、抑制细胞增殖。ACE2-Ang1-7-Mas轴的发现为RAS的研究、高血压等心血管疾病的防治和新药开发提供了新的思路和方向。     

作为肾素-血管紧张素系统调节器和SARS病毒受体的人血管紧张素转换酶2

人血管紧张素转换酶2(ACE2)是目前已知的惟一的人血管紧张素转换酶(ACE)的同源物,是一种新型的金属羧肽酶,很多特性与ACE截然不同.ACE2在肾素-血管紧张素系统(RAS)中具有独特的作用,调节心脏功能和机体血压.最近ACE2被鉴定为SARS病毒的功能受体.ACE2已经成为目前药物研发的新靶点.对ACE2的认识才刚刚开始,有待进-步深入研究.     

食品蛋白质中血管紧张素转化酶抑制肽的研究

血管紧张素转化酶Ⅰ (angiotensinIconvertingenzyme ,简称ACE)在人体血压调节过程中起重要的生理作用。源于食品蛋白质中的血管紧张素转化酶抑制肽 (angiotensinIconvertingenzymeinhibitorypeptides ,简称ACEIP)有明显的降血压作用 ,这些肽是通过抑制ACE的活性起降血压作用。文章中综述了来源于各种食品蛋白质的ACEIP的最新研究进展以及两种主要制备方法和评价方法 ,并对食品蛋白质中ACEIP的应用前景进行了展望     

汉族人群中血管紧张素转换酶抑制剂所致咳嗽与血管紧张素转换酶基因及缓激肽β2受体基因多态性的关系

目的:探讨汉族人群中血管紧张素转换酶抑制剂(ACEI)所致咳嗽与血管紧张素转换酶(ACE)基因及缓激肽β2受体(BDK-RB2)基因多态性的关系。方法:应用聚合酶链反应(PCR)方法,检测汉族人群中151例由于服用ACEI引起的咳嗽患者及151例未发生咳嗽的患者的ACE I/D及BDKRB2 C/T的多态性,并采用紫外法检测ACE活性。结果:发现ACE基因分布在咳嗽组中II型为47.0%,ID型为42.4%,DD型为10.6%;无咳嗽组分别为39.7%、47.0%、13.3%,两组相比其差异具有统计学意义(P<0.01);BDKRB2基因分布在咳嗽组中CC型为21.3%,CT型为50.0%,TT型为28.7%,无咳嗽组分别为22.5%、47.7%、29.8%,两组相比其差异无统计学意义(P>0.05);咳嗽组ACE活性水平为([28.3±10.1)U/L]明显低于无咳嗽组([40.2±9.4)U/L],两组相比其差异具有统计学意义(P<0.01)。结论:汉族人群中ACEI所致咳嗽与ACE基因多态性及血清ACE水平有关,BDKRB2 C/T与咳嗽间未发现有统计学意义的关联。     

血管紧张素转换酶2的功能和应用

人血管紧张素转换酶2（ACE2）是肾素-血管紧张素系统（RAS）的重要调节分子,它在控制心血管和血压的正常生理活动中具有重要的作用。此外,ACE2作为SARS病毒的受体,对于病毒的入侵起关键作用。目前ACE2已经被用于高血压和心血管相关疾病的药物靶标设计和基因治疗,随着研究的深入,ACE2在临床上的应用将更加广泛。     

猪肺血管紧张素转换酶的提纯

本文报道了猪肺血管紧张素转换酶(ACE)的提纯方法及其鉴定,并讨论了方法的改进。肺匀浆经1.6—2.6mol/L硫酸铵沉淀,Sephadex G-200凝胶过滤,DEAE-Sephaeel及羟基磷灰石柱层析步骤,从168克肺中获得4.5毫克酶蛋白纯品。活力回收45.2％,比活力15.6单位/毫克蛋白;和匀浆上清比较,提纯390倍。经聚丙烯酰胺凝胶电泳(pH8.3)鉴定为一条带。按SDS聚丙烯酰胺凝胶电泳(SDS-PAGE)测得其分子量为132,000道尔顿。酶蛋白在-30℃貯存10月,比活力丢失30％。     

Ketomethylureas. A New Class of Angiotensin Converting Enzyme Inhibitors

Abstract

The design rationale for a new series of tripeptide derived angiotensin converting enzyme (ACE) inhibitors, which we term “ketomethylureas”, is described. Analogs of tripeptide substrates (i.e. N-benzoyl-Phe-Ala-Pro) in which the nitrogen atom of the scissile amide bond and the adjacent asymmetric carbon atom of the penultimate amino acid residue are formally transposed give rise to this novel class of inhibitors. The most potent ketomethylureas inhibit ACE wtih I₅₀ values in the nM range.     

Angiotensin Converting Enzyme Inhibitors as Oxygen Free Radical Scavengers

The authors have compared the ability of two non-SH-containing angiotensin converting enzyme (ACE) inhibitors (enalaprilat and lisinopril) with an -SH containing ACE inhibitor (captopril) to scavenge the hydroxyl radical (OH). All three compounds were able to scavenge -OH radicals generated in free solution at approximately diffusion-controled rates (10¹⁰ M^-1s^-1) as established by the deoxyribose assay in the presence of EDTA. The compounds also inhibited deoxyribose degradation in reaction mixtures which did not contain EDTA but not so effectively. This later finding also suggests that they have some degree of metal-binding capability. Chemiluminescence assays of oxidation of hypoxanthine by xanthine oxidase in the presence of luminol, confirm that the three ACE inhibitors are oxygen free radical scavengers. Our results indicate that the presence of a sulphydryl group in the chemical structure of ACE inhibitors is not relevant for their oxygen free radical scavenging ability.     

血管紧张素转换酶纯化与性质研究

为了深入了解猪肺血管紧张素转换酶 (angiotensin converting enzyme,ACE)的性质和功能 ,对猪肺 ACE的分离纯化以及部分酶学性质进行了研究 .猪肺组织匀浆经 1 .6～ 2 .6mol/L硫酸铵分级沉淀等步骤后 ,利用亲和胶进行亲和层析分离 .2 0 0 g猪肺组织中提纯出 0 .79mg ACE,比活力 38.8U/mg,SDS- PAGE电泳鉴定为一条带 ,分子量约 1 80 k D,等电点 (p I)为 p H4.5,糖含量约 2 3.6% ,氨基酸组成分析发现猪肺 ACE分子中含有 1 346个氨基酸 ,其中酸性氨基酸含量较高 ,碘乙酸的修饰结果表明猪肺 ACE中巯基基团未参与酶的催化反应 .酶反应动力学结果显示 ,ACE催化 Fa PGG底物反应时的最适 p H大约为 p H 7.6,反应活化能 Ea=4.37× 1 0 4 J/mol,酶活性部位附近的组氨酸和具有类似 α-氨基性质的氨基酸可能参与了 ACE催化反应 .有关猪肺 ACE的基本生化性质、氨基酸组成以及酶学性质的结果 ,为今后深入研究奠定了基础 .     

Characterization of New Milk-derived Inhibitors of Angiotensin Converting Enzyme In Vitro and In Vivo

Inhibition of angiotensin converting enzyme (ACE) has been observed with a variety of different peptides, and peptide fragments with inhibitory capabilities have been identified within many different proteins, including milk proteins. The purpose of this study therefore was to identify new short peptides with inhibitory properties from the primary structure of milk proteins and to characterize them in vitro and in vivo, since no milk derived ACE inhibitors have previously been evaluated for their ability to inhibit ACE in vivo. In vitro, 8 of 9 dipeptides were found to be competitive inhibitors of ACE. The IC₅₀ was significantly lower when an angiotensin I-like substrate was used, than when a bradykinin-like substrate was used. Using three different in vivo models for ACE inhibition, a very moderate effect was observed for three of the new peptides, but only for up to 6 or 12 minutes. Nothing was observed with two reference compounds that are reported to be hypotensive ACE-inhibitors derived from milk proteins. This raises the question whether the mechanism of hypotensive action is straightforward inhibition of ACE in vivo.     

ACE基因多态性与高血压肾脏损害及PAI-1的关系

为探讨血管紧张素转换酶（ACE）基因多态性与高血压肾损害和纤溶酶原激活物抑制物-1（PAI-1）的关系,应用聚合酶链反应（PCR）检测96例正常人、67例高血压无肾脏损害患者和70例高血压伴肾损害患者的ACE基因型,采用ELISA法检测血浆PAI-1。ACE基因I/D多态性与高血压病无明显相关,但高血压肾损害患者DD基因型频率及D等位基因频率显著高于对照组和高血压无肾脏损害组,χ2值分别为6.8589、5.6162 和5.9085、5372。血浆PAI-1在DD型、ID型、II型高血压患者之间亦有显著性差异（P＜0.05）。ACE基因DD型可能是高血压肾损害的危险因素;ACE基因多态性与血浆PAI-1水平相关。 Abstract:The work is to explore the relationship between the polymorphism of angiotensin converting enzyme(ACE) gene and hypertensive kidney lesion/PAI-1 in hypertension patients.ACE genotyping with polymorase chain reaction (PCR) was performed in 96 unrelated healthy controls,67 hypertensives without kidney lesion and 70 hypertensives complicated with kidney lesion.The plasma PAI-1 were determined with ELISA.No significant differences could be detected between ACE gene I/D polymorphism and hypertension.However,the frequencies of DD genotype and deletion allele among the hypertensives complicated with kidney lesion were higher than those among the healthy controls and those among the hypertensives without kidney lesion."χ2" values were 6.8589,5.6162 and 5.9085,5.372 respectively.The plasma PAI-1 level showed significant differences among DD genotype,ID genotype and II genotype(P＜0.05).The DD genotype of ACE gene may be a risk for hypertensive kidney lesion.The plasma PAI-1 level is associated with ACE gene polymorphism.     

从米糠中提取降血管紧张素转换酶抑制剂

采用盐析法提取米糠蛋白,分别选用胃蛋白酶、胰蛋白酶、木瓜蛋白酶等单独或联合水解米糠蛋白,以从酶解米糠蛋白中分离获得具有血管紧张素转换酶（ACE）抑制活性的短肽组分。经Sephadex G-15凝胶层析和SP—Sephadex C-25离子交换层析分离各酶解组分,并检测各组分的ACE抑制活性。结果表明,米糠蛋白的酶解分离产物中含有较强ACE抑制活性的组分,其中经胃蛋白酶和胰蛋白酶共同水解时得到的小分子量寡肽组分的抑制活性最强,为后续对其进行结构分析奠定了基础。     

Oxidant Stress and Glomerular Prostanoid Production: Influence of Angiotensin Converting Enzyme Inhibition

1. The effect of H₂O₂ (4.7 × 10^-9 4.7 × 10^-3M) on prostanoid production by isolated glomeruli from normotensive (WKY) and, spontaneously hypertensive rats (SHR) has been studied.

2. Oxidant stress significantly increased synthesis of prostaglandin E₂(PGE₂), I₂(PGI₂)and thromboxane A₂ (TxA₂) by glomeruli from both strains whereas the ratio (PGE₂ + PGI₂)/TxA₂ increased in only SHR.

3. Pre-incubation of glomeruli with the angiotensin converting enzyme inhibitors captopril or lisinopril, had virtually no effect on H₂O₂-induced synthesis of individual prostanoids nor on the ratio (PGE₂ + PGI₂)/TA₂ by glomeruli from either WKY or SHR.

4. The findings suggest that H₂O₂-induced changes in glomerular function may be mediated, in part, by PGs but fail to support the suggestion that the ability of ACEI to protect glomeruli from H₂O₂-induced damage is determined by PGs.     

血管紧张素转换酶抑制剂的分子设计

目的:以血管紧张素转换酶(ACE)为受体靶蛋白,设计相应的抑制剂分子。方法:采用计算机辅助药物分子设计的方法,在分析已有的关于ACE及其抑制剂的基础上,确定分子设计软件LigBuilder中的相关参数。结果:设计得出了1500个配体分子,并从中筛选出了1个各项得分最高的新型血管紧张素转换酶抑制剂分子,其分子式为C27H36N2O3,分子量为436,logP值为4.95,与受体靶蛋白ACE的结合力得分为11.71。结论:从计算得分来看,所设计出的分子与ACE的亲和性好,且脂溶性高,为发掘高活性的降压药物提供了线索。     

Characterization of Neuronal and Endothelial Forms of Angiotensin Converting Enzyme in Pig Brain

The molecular forms of angiotensin converting enzyme (ACE; EC 3.4.15.1) in preparations of pig brain cortical microvessels and striatal synaptosomal membranes have been identified by immunoelectrophoretic blot analysis. The cortical microvessels contained only the endothelial form of the enzyme, Mr 180,000, which comigrated with pig kidney ACE on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In contrast, the synaptosomal membranes contained only a smaller form of ACE, Mr 170,000, which represents the neuronal form of the enzyme. No significant differences in inhibitor sensitivity or substrate specificity were detected between the two forms of ACE. In particular, neurokinin A was resistant to hydrolysis by either microvessel or synaptosomal membrane ACE, and the pattern of hydrolysis of substance P by the two preparations was identical.     

Angiotensin Converting Enzyme in Alzheimer''s Disease: Increased Activity in Caudate Nucleus and Cortical Areas

The activity of the dipeptidyl carboxypeptidase, angiotensin converting enzyme, was assayed in several brain regions of patients dying with Alzheimer's disease and compared to that of appropriately age-matched controls. Enzyme activity was found to be elevated by 44% and 41% in the medial hippocampus and parahippocampal gyrus, respectively, and by 27% and 29% in the frontal cortex (area 10 of Brodman) and caudate nucleus, respectively, in Alzheimer's disease patients. Converting enzyme activity did not differ from controls in the nucleus accumbens, substantia nigra, temporal cortex, anterior or posterior hippocampus, amydgala, and septal nuclei.