阻断肾素血管紧张素系统防治2型糖尿病

最近的多项临床研究显示阻断肾素血管紧张素系统（renin angiotensin system RAS）可以显著降低2型糖尿病的发病风险,并延缓其病程及并发症的出现.对高血压患者的CAPPP（卡托普利防治计划）和VALUE（缬沙坦长期抗高血压治疗评估研究）等研究显示卡托普利或缬沙坦治疗后显著降低2型糖尿病的发病率。对老年患者的SCOPE（老年人认知与预后研究）显示坎地沙坦与安慰剂对照示糖尿病的发病率下降了25％。     

肾素-血管紧张素系统与糖尿病脑病

肾素-血管紧张素系统是体内重要的内分泌系统之一,通常认为其功能主要是调节血压和保持水电解质平衡.但近年的研究证实该系统还参与学习、记忆等认知功能的调节,并在糖尿病脑病的发病过程中发挥重要作用.例如:血管紧张素(Ang)Ⅱ可以抑制乙酰胆碱的释放、抑制长时程增强(LTP)的诱导、干扰胰岛素的信号转导、激活体内的氧化应激以及减少中枢的血供;AngⅣ可以促进乙酰胆碱的释放,易化LTP;Ang-(1-7)可以易化LTP,还能改善中枢血流.这些发现为糖尿病脑病的防治提供了新思路.     

肾素-血管紧张素系统与脂肪代谢研究进展

肾素-血管紧张素系统(RAS)的多种成分可在脂肪组织中表达。在鼠类动物模型中,RAS促进脂肪细胞生长、分化,甘油三酯储存,细胞肥大,体脂沉积;而在人类成熟脂肪细胞,血管紧张素Ⅱ抑制前体脂肪细胞分化,使脂肪异位沉积在肝脏、骨骼、胰岛组织,从而形成胰岛素抵抗。抑制RAS系统的药物,如血管紧张素转换酶抑制剂、血管紧张素受体拮抗剂可能改善肥胖相关的高血压、脂代谢紊乱、胰岛素抵抗,从而减少2型糖尿病的发生。     

胰腺肾素-血管紧张素系统对胰岛β细胞功能的影响

近年研究显示胰腺局部组织存在肾素-血管紧张素系统,对胰岛β细胞功能有着直接或间接的影向,其主要活性成分为血管紧张素Ⅱ.后者在胰腺局部表达并活化,与其受体结合发挥生物学作用.可以改变胰腺局部血流动力学,增强胰腺局部氧化应激及炎性反应,从而通过活性氧簇和炎性反应因子对胰岛β细胞造成损伤,同时可抑制胰岛素的生物合成和分泌,诱导胰岛β细胞凋亡并抑制其增殖,使其数量减少,并影响β细胞的形态与结构、增强纤维化程度,从而促进糖尿病的发生、发展.     

脂肪组织局部肾素-血管紧张素系统的调节及其在糖尿病中的作用

脂肪组织局部存在肾素-血管紧张素系统(RAS)中几乎所有的组分,这些组分不仅构成局部RAS,而且是循环中RAS各成分的重要来源.多种因素包括肥胖、胰岛素等均可以影响脂肪组织中RAS各成分的表达.脂肪组织局部RAS活性增加,可作用于脂肪细胞,抑制脂肪细胞分化及脂质代谢,并影响脂肪细胞因子分泌,同时血管紧张素可作用于周围组...     

胰腺组织肾素-血管紧张素系统及其作用

<正>肾素-血管紧张素系统(renin angiotensin system,RAS)在调节机体血压、血容量和水电解质平衡方面起着重要的作用。近年研究发现,许多组织器官都存在局部RAS,包括心、肺、肝、肾、脂肪、肾上腺和     

脂肪组织局部肾素-血管紧张素系统的调节及其在糖尿病中的作用

脂肪组织局部存在肾素-血管紧张素系统(RAS)中几乎所有的组分,这些组分不仅构成局部RAS,而且是循环中RAS各成分的重要来源.多种因素包括肥胖、胰岛素等均可以影响脂肪组织中RAS各成分的表达.脂肪组织局部RAS活性增加,可作用于脂肪细胞,抑制脂肪细胞分化及脂质代谢,并影响脂肪细胞因子分泌,同时血管紧张素可作用于周围组织,通过加重炎性反应和氧化应激等途径,导致胰岛素抵抗,参与糖尿病的病理过程.     

肾素-血管紧张素系统的研究进展

肾素血管紧张素系统一直是人们研究的热点,现就肾素血管紧张素系统的组成成分、代谢途径及其生物学作用作一介绍。     

肾素血管紧张素系统与糖尿病肾病

组织肾素－血管紧张素系统的发现及研究进展，使人们对该系统有了进一步的认识。本文扼要综述肾脏肾素－血管紧张素研究近况及其与糖尿病肾病发生，发展的可能关系。     

肾素-血管紧张素系统与脂肪代谢及胰岛素抵抗的关系

近年来,内分泌研究领域的研究热点及重大进展之一,就是证实了脂肪组织的内分泌功能及其与肥胖相关疾病的关系,通过小鼠模型及人类的分子生物学研究表明,局部脂肪组织内存在相当完整的肾素-血管紧张素系统(RAS),其主要效应分子血管紧张素Ⅱ(Ang Ⅱ)可通过内分泌、旁分泌、自分泌作用参与局部体脂调节,影响脂肪代谢,形成胰岛素抵抗,表现为代谢综合征(MetS).     

肾素-血管紧张素系统与糖尿病

肾素-血管紧张素系统(RAS)在糖尿病的发生、发展中有重要作用.今年的国际糖尿病联盟(IDF)第20次学术会议专题报道了糖尿病人群的RAS系统.简而言之,最有效的延缓糖尿病肾病进展的途径是阻滞RAS.大量临床研究也已经证实了阻滞RAS治疗糖尿病肾病的疗效.肾素抑制途径的研究,为防治肾损害提供了一个新的治疗方向.     

Renin-angiotensin system inhibition prevents type 2 diabetes mellitus. Part 2. Overview of physiological and biochemical mechanisms

The inhibition of the renin-angiotensin system (RAS) with either angiotensin converting enzyme inhibitors (ACEIs) or AT1 angiotensin receptor blockers (ARBs) consistently and significantly reduces the incidence of type 2 diabetes in patients with hypertension or congestive heart failure. The mechanisms underlying this protective effect appear to be complex and may involve an improvement of both insulin sensitivity and insulin secretion. These two effects may result, at least in part, from the well known effects of these pharmacological agents on the vascular system on the one hand, on the ionic balance on the other hand. Indeed, the vasodilation induced by ACEIs or ARBs could improve the blood circulation in skeletal muscles, thus favouring peripheral insulin action, but also in the pancreas, thus promoting insulin secretion. Preserving cellular potassium and magnesium pools by blocking the aldosterone effects could also improve both cellular insulin action and insulin secretion. However, besides these classical effects, new mechanisms have been recently suggested. A direct effect of the inhibition of angiotensin and/or of the enhancement of bradykinin on various steps of the insulin cascade signalling has been described as well an increase in GLUT4 glucose transporters after RAS inhibition. Furthermore, it has been demonstrated that angiotensin II inhibits adipogenic differentiation of human adipocytes via A1 receptors and, therefore, it has been hypothesised that RAS blockade may prevent diabetes by promoting the recruitment and differentiation of adipocytes. Finally, some lipophilic ARBs appear to induce PPAR-gamma activity in the adipose tissue. Hence, the protection against type 2 diabetes observed after RAS inhibition may be partially linked to a thiazolidinedione-like effect. In conclusion, numerous physiological and biochemical mechanisms could explain the protective effect of RAS inhibition against the development of type 2 diabetes in individuals with arterial hypertension or congestive heart failure. What might be the main mechanism in the overall protection effect of ACEIs or ARBs remains an open question.     

Renin-angiotensin system inhibition prevents type 2 diabetes mellitus. Part 1. A meta-analysis of randomised clinical trials

Most individuals with arterial hypertension or congestive heart failure are insulin-resistant and at a higher risk of developing type 2 diabetes (T2DM). The inhibition of the renin-angiotensin system (RAS), using an angiotensin converting enzyme inhibitor (ACEI) or a selective angiotensin receptor AT1 blocker (ARB), may exert favourable metabolic effects capable of preventing T2DM in high risk individuals. We performed a meta-analysis of randomised clinical trials (RCTs) assessing the effects of RAS inhibition on the incidence of new cases of T2DM in patients with arterial hypertension or congestive heart failure. Ten RCTs with cardiovascular prognosis as primary endpoints analysed the incidence of T2DM as secondary endpoints or as post-hoc analysis after a mean follow-up of 1 to 6 years: five with an ACEI and five with an ARB, compared with a placebo (n = 4) or a reference drug (beta-blocker or diuretic: n = 5; amlodipine: n = 2). Eight RCTs concerned hypertensive patients: STOP Hypertension-2 (lisinopril or enalapril vs beta-blocker or diuretic), CAPPP (captopril vs thiazide or beta-blocker), HOPE (ramipril vs placebo), ALLHAT (lisinopril vs chlorthalidone and lisinopril vs amlodipine), LIFE (losartan vs atenolol), SCOPE (candesartan vs placebo), ALPINE (candesartan vs placebo) and VALUE (valsartan vs amlodipine). Two RCTs concerned patients with congestive heart failure: SOLVD (enalapril vs placebo) and CHARM-overall programme (candesartan vs placebo). Overall, 2 675 new cases of T2DM (7.40%) were observed in the group of 36 167 patients receiving a treatment with ACEI or ARA as compared with 3 842 events (9.63%) in the group of 39 902 control patients. A mean weighed relative risk reduction of new T2DM of 22% (95% CI: 18, 26; p < 0.00001) was observed after RAS inhibition. The beneficial effect was similar with ACEIs and with ARBs as well as in patients with hypertension and in those with heart failure, and was also present whatever the comparator (placebo or beta-blockers/diuretics or amlodipine). The number needed-to-treat to avoid one new case of T2DM averaged 45 patients over 4-5 years. In conclusion, RAS inhibition consistently and significantly reduces the incidence of T2DM in individuals with arterial hypertension or with congestive heart failure. Considering the pandemic of T2DM, such pharmacological approach deserves further attention among the strategies aiming at preventing T2DM.     

肾素血管紧张素系统与微炎症

高血压、糖尿病、脂质代谢紊乱和肥胖常常簇集出现而形成代谢综合征,严重影响公众的健康水平。近年来,代谢性疾病的微炎症背景备受学者关注,微炎症状态与代谢性疾病的发生发展密切关联。肾素一血管紧张素系统（RAS）,除了血流动力学调节作用外,在微炎症反应中也发挥重要的作用。阻断RAS,对代谢性疾病具有一定的保护作用。目前已证实,RAS主要通过血管紧张素转换酶一血管紧张素1I-ATl受体（ACE-AnglI-ATlR）轴和ACE2-Ang（1-7）-Mas轴发挥作用,这两条途径具有相反的生物学活性,后者对前者有拈抗作用。血管紧张素Ⅱ（AngII）由血管紧张素Ⅱ受体介导通过多种机制发挥致炎作用,而Ang（1-7）可以拮抗AngII,抑制炎症反应。本文就RAS参与微炎症反应的相关机制做一综述。     

Renin-angiotensin system revisited

New components and functions of the renin-angiotensin system (RAS) are still being unravelled. The classical RAS as it looked in the middle 1970s consisted of circulating renin, acting on angiotensinogen to produce angiotensin I, which in turn was converted into angiotensin II (Ang II) by angiotensin-converting enzyme (ACE). Ang II, still considered the main effector of RAS was believed to act only as a circulating hormone via angiotensin receptors, AT1 and AT2. Since then, an expanded view of RAS has gradually emerged. Local tissue RAS systems have been identified in most organs. Recently, evidence for an intracellular RAS has been reported. The new expanded view of RAS therefore covers both endocrine, paracrine and intracrine functions. Other peptides of RAS have been shown to have biological actions; angiotensin 2-8 heptapeptide (Ang III) has actions similar to those of Ang II. Further, the angiotensin 3-8 hexapeptide (Ang IV) exerts its actions via insulin-regulated amino peptidase receptors. Finally, angiotensin 1-7 (Ang 1-7) acts via mas receptors. The discovery of another ACE2 was an important complement to this picture. The recent discovery of renin receptors has made our view of RAS unexpectedly complex and multilayered. The importance of RAS in cardiovascular disease has been demonstrated by the clinical benefits of ACE inhibitors and AT1 receptor blockers. Great expectations are now generated by the introduction of renin inhibitors. Indeed, RAS regulates much more and diverse physiological functions than previously believed.     

肾素-血管紧张素系统与组织纤维化

肾素-血管紧张素系统（RAS）在心、脑、肾、肺等器官的组织纤维化病理过程中发挥重要作用。RAS与组织纤维化的发生、发展密切相关,血管紧张素转换酶抑制剂或血管紧张素Ⅱ的Ⅰ型受体拮抗剂可防治组织纤维化的进程。     

肾素-血管紧张素系统与肺部疾病

肾素-血管紧张素系统(renin-angiotensin system,RAS)具有调节血压和水钠平衡的生理作用.近年来,研究发现RAS在多种肺部疾病中发挥作用,例如肺动脉高压、肺纤维化、肺血栓栓塞症和急性呼吸窘迫综合征.最近发现RAS中的血管紧张素转化酶2(angiotensin-converting enzyme 2,ACE2)是SARS冠状病毒的受体,且病毒感染后ACE2下调可能是SARS患者肺损伤显著加重的原因.这些发现提示RAS与肺部疾病存在重要关系.     

肾素-血管紧张素系统与肺动脉高压

肺动脉高压(pulmonary hypertension,PH)是一种由异源性疾病和不同发病机制引起的,以肺动脉压力增高为表现的疾病状态,严重者可出现右心衰竭。目前的治疗方式虽然可缓解 PH 患者的部分症状,并在一定程度上延长患者的寿命,但 PH 仍然是一种死亡率极高的疾病,所以亟需发现新的安全有效的治疗方法。研究表明,肾素-血管紧张素系统(renin-angiotensin system,RAS)参与了 PH 的发病过程。该系统由促进血管收缩及增殖的血管紧张素转换酶-血管紧张素Ⅱ-血管紧张素Ⅱ受体1(angiotensin converting enzyme-angiotensinⅡ-angiotensinⅡ receptor 1,ACE-AngⅡ-AT1R)轴与抗血管收缩及增殖的血管紧张素转换酶2-血管紧张素(1-7)-Mas[angiotensin converting enzyme 2-angiotensin (1-7)-Mas,ACE2-Ang-(1-7)-Mas]轴组成。ACE-AngⅡ-AT1R 轴是促进 PH 病情发展的重要机制,而ACE2-Ang-(1-7)-Mas 轴因可以拮抗 ACE-AngⅡ-AT1R 轴的作用,成为 PH 治疗的研究热点。