他汀类药物降脂外作用的研究进展

10年前,《美国心脏病学杂志》主编Roberts教授曾把20世纪90年代的他汀类药物和40年代的青霉素相媲美,认为他汀类药物对心血管病的治疗就如同青霉素治疗感染性疾病一样神奇。随着他汀类药物的广泛应用,其强大的降脂外功能逐渐被认识,本文综述他汀类药物降脂外作用的研究进展。     

他汀类药物抗动脉粥样硬化研究进展

近年来,随着人们生活水平的提高和工作节奏的加快,心脑血管病的发病率和病死率都呈明显的上升态势.动脉粥样硬化是心脑血管病的主要病理基础,引起动脉粥样硬化的危险因素很多,其中脂质代谢紊乱甚为重要.3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶抑制药（他汀类）是目前临床上应用最为广泛的调血脂药物，其降低血浆总胆固醇和低密度脂蛋白的作用已为大量临床研究所证实。目前研究认为，他汀类对心脑血管病的治疗作用还得益于多种非调脂作用，包括改善血管内皮功能、抑制血栓形成、抗炎作用、抗氧化和稳定动脉粥样硬化斑块等，他汀类的非调脂作用可能在动脉粥样硬化的防治中占有重要地位。     

他汀类药物降脂与非降脂作用

1976年从真菌代谢产物中提出第一个他汀类分子meuastatiin,标志着他汀类降脂药的问世,为凋节血脂延缓动脉粥样硬化开辟了一个新纪元。近年来证实他汀类药物降脂幅度大、速度快、耐受性好,并具有改善血管内皮,抑制血管平滑肌细胞的增殖和迁移,降低心脑血管疾病患者的卒中发生率,抗血小板聚集、抗血栓形成,对心肌细胞的保护等作用。     

他汀类药物降脂外作用

随着医学模式的改变,循证医学的问世,近十余年来,已有大规模的临床实验研究证实他汀类药物除具有良好的降脂作用外,还有许多非降脂作用,比如:降压、防止心室肥厚,显著降低冠心病患者的总病死率,减少心肌梗死,血运重建术、中风和周围血管疾病的发生及抗炎、稳定冠脉斑块的作用.这些非降脂作用很可能在冠心病或其他疾病的防治中占重要位置.     

他汀类药物的非降脂作用

在过去的十几年中，他汀类药物（ＨＭＧ—ＣＯＡ还原酶抑制剂）以其疗效确切，不良反应少，耐受性好，为广大高脂血症患者带来了福音。同时，广大医务工作者还发现了他汀类药物存在非降脂作用的其他益处。１ 稳定斑块 动脉粥样硬化斑块由脂质核和纤维帽组成，前者中所含的Ｔ－淋巴细胞所释放的γ－干扰素和其他细胞因子可抑制平滑肌细胞（纤维帽内）合成胶原和弹性纤维，巨噬细胞吞噬脂质后形成泡沫细胞能释放蛋白酶，以分解胶原和弹性纤维。由此可见，平滑肌细胞受抑制易使斑块不稳定．普伐他汀稳定斑块作用表现在：（１）不抑制平滑肌细胞…     

他汀类药物在降脂作用外的应用新进展

他汀类药物在治疗血清胆固醇升高和血清低密度脂蛋白(LDL—C)方面的作用已被广大的医生和患者所接受和认可，并且在应用过程中还发现了他汀类药物具有其他的临床新用途。现结合文献进行分析和归纳如下：     

他汀类药物的非降脂作用

综述他汀类药物抗骨质疏松、抗血栓作用、对肾脏的保护作用、对心肌结构和功能的保护作用等非降脂作用。     

他汀类药物非降脂作用研究新进展

他汀类降脂药通过抑制3-羟基-甲基戊二酰辅酶A(HMG-COA)还原酶而起到降脂作用。主要包括洛伐他汀、辛伐他汀、普伐他汀、阿托伐他汀等多种药物,被广泛应用于血脂异常的相关性疾病,特别是动脉粥样硬化,高血压和冠心病等心血管疾病。近年来发现他汀类药物的作用除降脂以外还有多种作用,包括提高一氧化氮生物利用度、修复受损内皮、抗炎、抗氧化、促新生血管生成、抗血小板聚集、稳定动脉粥样硬化(AS)斑块、抑制心肌肥厚,抗心律失常[1]等。本文     

他汀类药物的非降脂作用

他汀类药物又称羟甲基戊二酸单酰辅酶A(HMG-CoA)还原酶抑制药.其主要机制是抑制胆固醇合成途径的HMG-CoA还原酶,阻止该酶催化产物甲羟戊酸的合成.临床应用显示此药具有安全有效的调整胆固醇和甘油三酯水平的作用;同时发现该药还具有诸多非降脂作用,如有抗骨质疏松、抗炎、抗肿瘤、抗病毒,降低脂蛋白(a)等作用.显示出临床多方面的应用价值.     

他汀类药物在呼吸系统疾病中的作用

目的:为认识他汀类药物在呼吸系统疾病中的作用提供参考。方法:对近年来国内外有关他汀类药物的研究文献进行检索、分析和归纳。结果:在慢性呼吸系统疾病治疗方面,如慢性阻塞性肺疾病、哮喘、肺损伤、低氧性肺动脉高压、肺心病、矽肺等,他汀类药物具有良好的抗炎作用。结论:他汀类药物有较强的抗炎作用和独立的血管保护效应,在呼吸系统疾病的治疗中发挥了一定的作用。     

Cardiovascular protective effects of resveratrol

Resveratrol (3,4',5-trihydroxy-trans-stilbene), a phytoalexin found in grape skins, peanuts, and red wine, has been reported to have a wide range of biological and pharmacological properties. It has been speculated that at low doses (such as consumed in the common diet) resveratrol may have cardioprotective activity. In this article we describe recent in vitro and in vivo studies in animal models. The results of these studies suggest that resveratrol modulates vascular cell function, inhibits LDL oxidation, suppresses platelet aggregation and reduces myocardial damage during ischemia-reperfusion. Although the reported biological data indicate that resveratrol is a highly promising cardiovascular protective agent, more studies are needed to establish its bioavailability and in vivo cardioprotective effects, particularly in humans.     

二甲双胍的心血管保护作用

二甲双胍(Metformin)属双胍类药物,作为口服降糖药应用于2型糖尿病(T2DM)已有50年的历程,其降糖作用已得到公认。近年越来越多的研究发现,二甲双胍具有降糖以外的心血管保护作用,能抑制动脉粥样硬化(Atherosclero-sis,AS)、心衰、心肌梗死等心血管病的发生和发展。但二甲双胍确切的心血管保护机制仍不明确,本文综述了二甲双胍对心血管疾病的作用,并探讨其可能的作用机制。     

黄芪甲苷对心血管的保护作用(英文)

黄芪甲苷作为中药黄芪的主要有效成分,具有舒张血管,保护血管内皮细胞,抗炎,抗病毒,正性肌力等多方面作用,这些作用是通过抗氧化损伤、清除氧自由基、调节钙稳态、抗线粒体损伤等途径实现的。黄芪甲苷目前已有效用于治疗冠心病、心力衰竭、高血压、心肌炎等心血管疾病,其对心血管的保护作用和机制有待进一步研究。     

心肌梗塞后倍他乐克与他汀类药物对心脏保护作用的研究

目的：探讨心肌梗塞后,倍他乐克和他汀类药物对心脏的保护作用。方法：选取于2012年1月～2014年1月来我院诊治的心肌梗塞患者90例,平均分为两组,即观察组和对照组。对照组采用常规方法治疗;观察组在常规治疗的基础上,加用倍他乐克与他汀类药物治疗;观察、比较两组的治疗效果。结果：治疗后,观察组总有效率达91.1%,对照组总有效率达75.6%。两组比较,观察组治疗总有效率明显优于对照组（P<0.05）。心功能方面,观察组中LVADD小于对照组,差异具有统计学意义（P＜0.05）,E/A明显高于对照组（P＜0.01）,HR明显低于对照组（P＜0.01）。血脂方面,观察组中TC和LDL-C两项指标明显低于对照组（P＜0.01）,TG与对照组比较无明显差异（P＞0.05）。结论：倍他乐克与他汀类药物对于心肌梗塞后患者具有较好的心脏保护作用,值得临床推广。     

释放一氧化氮型他汀类药的血管保护作用

他汀类(statins)药物是3-羟基-3-甲基戊二酰辅酶A(HMG-CoA)还原酶抑制剂,通过抑制HMG-CoA转化为甲基二羟戊酸(mevalonate)降低血中胆固醇。越来越多的研究表明,他汀类药物具有多效性药理学作用〔1〕,其中,部分通过一氧化氮(NO)对动脉粥样硬化和血管炎性过程有调节作用〔2〕。NO与许多生理调节功能有关联,如调节心血管自稳状态以及炎症、宿主防御反应和血管平滑肌细胞(SMC)增殖等。因此,为了增强他汀类药物选择性的非降脂作用,将缓慢释放NO的化学结构引入他汀类药物的骨架结构上,构成释放一氧化氮型他汀类药(NO-statins)。Ongini E…     

Cardiovascular effects of DPP-4 inhibition: beyond GLP-1

Dipeptydil-peptidase-4 (DPP-4) inhibitors are available as oral anti-hyperglycemic drugs for the treatment of type 2 diabetes. Their metabolic effect is mediated through sparing incretin hormones (such as glucagon-like peptide-1, GLP-1) from the rapid degradation by DPP-4. In turn, GLP-1 improves meal-stimulated insulin secretion by pancreatic β-cells thus reducing hyperglycemia. It has been shown that GLP-1 signaling is also active in the cardiovascular system, where it may exert beneficial effects. However, DPP-4 has several non-incretin substrates, and its immunomodulatory activity is known from decades. DPP-4 physiologically cleaves cytokines, chemokines and neuropeptides involved in inflammation, immunity, and vascular function. Owing to these off-target mechanisms, DPP-4 inhibitors hold promise for cardiovascular protection, but may also face unexpected side effects. Herein, we review available data on the cardiovascular effects of DPP-4 inhibitors, with a special interest in GLP-1-independent mechanisms. The modulation of endothelial progenitor cells, inflammatory pathway and ischemic response emerges as the major cardiovascular target of DPP-4 inhibitors.     

他汀类降脂药的抗炎作用

<正>他汀类药物,即3-羟基-3-甲基戊二酰辅酶A (HMA-CoA)还原酶抑制剂,可减少动脉粥样硬化的形成和心血管事件的发病率及死亡率。上述作用源自该类药物对胆固醇代谢的影响以及下调低密度脂蛋白的合成。目前越来越多的证据显示,除上述作用外,他汀类药物还有更广泛的作用,其中包括对炎症途径的影响,具有免疫调节活性,在许多炎症性疾病中表现出一定的治疗作用。     

Antioxidative effects of statins

Abstract HMG CoA reductase inhibitiors (statins) have been shown to be effective lipid lowering agents and are beneficial in the primary and secondary prevention of coronary heart disease. However, the overall benefits observed with statins appear to be greater than what might be expected from changes in lipid levels alone and the positive effects have only partially been reproduced with other lipid lowering drugs, suggesting effects in addition to cholesterol lowering. In experimental models, many of the cholesterol-independent effects of statins are mediated by inhibition of isoprenoids, which serve as lipid attachments for intracellular signalling molecules such as small Rho guanosine triphosphate-binding proteins, whose membrane localization and function are dependent on isoprenylation. This review summarizes the effects of statins on endothelial function and oxidative stress.     

Antioxidant effects of statins

Statins, a group of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, are widely used in clinical practice for their efficacy in producing significant reductions in plasma cholesterol and LDL cholesterol and in reducing morbidity and mortality from cardiovascular disease. However, several large clinical trials have suggested that the cholesterol-lowering effects of statins may not completely account for the reduced incidence of cardiovascular disease seen in patients receiving statin therapy. A number of recent reports have shown that statins may also have important antiinflammatory effects, in addition to their effects on plasma lipids. Since inflammation is closely linked to the production of reactive oxygen species (ROS), the molecular basis of the observed antiinflammatory effects of statins may relate to their ability block the production and/or activity of ROS. In this review, we will discuss both the inhibition of ROS generation by statins, through interference with NAD(P)H oxidase expression and activity, and the actions of statins that serve to blunt the damaging effects of these radicals, including effects on antioxidant enzymes, lipid peroxidation, LDL cholesterol oxidation and nitric oxide synthase. These antioxidant effects of statins likely contribute to their clinical efficacy in treating cardiovascular disease as well as other chronic conditions associated with increased oxidative stress in humans.