肾素-血管紧张素系统在慢性环孢素肾病中的作用

目的测定肾素、血管紧张素Ⅱ(AngⅡ)在慢性环孢素(CsA)肾病肾移植患者肾组织、血浆中的水平,探讨肾素-血管紧张素系统(RAS)在慢性CsA肾病中的作用.方法(1)采用免疫组化、放射免疫和荧光偏振法,测定13例慢性CsA肾病患者肾组织中肾素表达及血浆AngⅡ、CsA早晨服药后2 h血浓度(C2)水平,并结合临床表现进行分析.(2)体外培养人脐静脉内皮细胞株(HUVEC)、大鼠系膜细胞株(MC),经不同浓度CsA(0、250、500、1000 μg/L)孵育细胞后,用免疫组化和放免方法测定肾素的表达及AngⅡ的含量.结果慢性CsA肾病组肾素指数与对照组比较显著增高(P＜0.01);血浆AngⅡ、C2水平高于对照组,但无显著性差异[(122.69±26.73)pg/ml比(121.88±36.35)pg/ml,P=0.977,(719.04±55.89)pg/ml比(658.80±90.78)pg/ml,P=0.196].CsA在一定浓度范围内呈剂量依赖刺激HUVEC、MC分泌AngⅡ及上调肾素的表达.结论移植肾活检可避免慢性CsA肾病漏诊或误诊.慢性CsA肾病肾移植患者肾组织局部RAS活化,导致血浆AngⅡ水平与肾组织局部表达不一致.CsA刺激血管内皮细胞、肾小球系膜细胞分泌AngⅡ,上调肾素的表达.阻断RAS可能有益于延缓慢性CsA肾病的进程.     

肾素-血管紧张素系统组成的新认识及其在肾脏的作用

肾素-血管紧张素系统（rennin angiotensin system，RAS）是最重要的心血管系统体液调节机制之一，最近发现了这一系统的许多新成员，包括AngⅡ受体、ACE2、Ang（1～7），这些物质的发现和对其生理意义的研究让我们对RAS有了许多新的认识。RAS对肾脏作用的研究也日益增多，RAS对肾脏的非血流动力学作用，AngⅡ受体、ACE2和Ang（1-7）在肾脏中的作用成为目前研究的热点。     

肾素-血管紧张素系统与急性胰腺炎

肾素 血管紧张素系统 (RAS)是人体内一个经典的调节血压和体液平衡的系统 ,近年来在包括胰腺在内的许多组织中发现有局部RAS存在。胰腺RAS含有许多非经典的RAS组分 ,能影响胰腺的内外分泌功能。在急性胰腺炎中 ,RAS可能通过调节血供、氧分压、自由基、炎症介质等机制发挥一定作用 ,抑制其活性可能对胰腺有保护效果 ,对其进行更深入的研究将为临床治疗提供一些新的思路。     

胰腺局部组织肾素-血管紧张素系统研究进展

肾素 -血管紧张素系统 (ＲＡＳ)作为循环的激素系统 ,通过对心血管、肾脏、神经系统等的影响 ,在维持血压及水电解质平衡方面起着重要的调节作用 ,其效应肽血管紧张素Ⅱ (ＡＮＧⅡ )通过相应的受体ＡＴ1、ＡＴ2 发挥关键作用[1] 。随着认识的深入 ,人们发现相对于全身循环的、系统的ＲＡＳ ,多个组织器官存在着局部组织的ＲＡＳ ,并可以通过自分泌以及旁分泌等方式参与多种物质表达的调控、细胞的生长、凋亡、纤维化以及炎症反应 ,以适应各自不同的功能调节[2 ] 。近年来随着细胞和分子生物学技术的发展 ,对于胰腺局部组织ＲＡＳ的研究也取…     

肾素-血管紧张素系统组成的新认识及其在肾脏的作用

肾素-血管紧张素系统(rennin angiotensin system,RAS)是最重要的心血管系统体液调节机制之一,最近发现了这一系统的许多新成员,包括AngⅡ受体、ACE2、Ang(1~7),这些物质的发现和对其生理意义的研究让我们对RAS有了许多新的认识。RAS对肾脏作用的研究也日益增多,RAS对肾脏的非血流动力学作用,AngⅡ受体、ACE2和Ang(1~7)在肾脏中的作用成为目前研究的热点。     

血浆肾素-血管紧张素系统、一氧化氮在心包炎中的变化及作用

目的探讨血浆肾素-血管紧张素系统(RAS)、一氧化氮(NO)在心包炎病变过程中的变化及作用.方法 21只雄性家兔随机分为两组,实验组:11只,心包腔内注入40%尿素,2ml/kg;对照组:10只,心包腔内注入等量生理盐水.分别于术前和术后1、4、7、10、15、21天采血测定血浆肾素活性(RA)、血管紧张素Ⅱ(ANGⅡ)和NO的浓度,观察心包、心肌、肺和肝的病理改变.结果术后实验组血浆RA、ANGⅡ和NO浓度较术前均升高,术后7～21天与对照组同时点比较差别具有显著性意义(P<0.01);实验组兔心包增生增厚、心肌变性、肺淤血和肝淤血.结论心包炎病变过程中血浆RAS、NO浓度均升高,一方面NO与RAS相拮抗,另一方面NO和RAS共同介导心包、心肌、肺、肝等器官的损伤.     

肾素-血管紧张素系统阻断与肾脏病

通过介绍血管紧张素Ⅱ（ＡⅡ）的产生途径、受体亚型等有关进展,比较阻断肾素血管紧张素系统不同方法的异同,探讨ＡⅡ１型受体拮抗剂（ＡＴ１ＲＡ）在降低血压及延缓肾脏疾病进展中的作用     

肾素-血管紧张素系统在糖尿病肾病研究中的新进展

近年来糖尿病(特别是2型)的发生率有逐步上升趋势,而糖尿病肾病(DN)又是最常见的并发症之一,累及率约为30%～35%。一旦肾脏累及出现持续性蛋白尿,则肾脏病变往往不可逆转,最终在较短时间内进入终末期肾功能衰竭(ESRD)。目前由于DN所致ESRD,需行维持透析的患者数每年都在增加,为之耗费大量人力、物力、财力。可见对于DN发病机制和预防治疗的研究显得尤为重要。高血糖造成肾脏血流动力学改变以及葡萄糖本身代谢异常所致的一系列后果为造成肾脏病变的基础;众多生长因子、细胞因子被激活则是病变形成的直接机制。其中有关肾素-血管紧张素…     

肾素血管紧张素系统与腹膜纤维化

肾素血管紧张素系统（RAS）是机体调节血管张力和钠水代谢的内分泌系统，随血液循环发挥作用。在慢性腹膜透析所致腹膜纤维化发病过程中，腹膜局部RAS激活，血管紧张素Ⅱ（ATⅡ）增加，促进转化生长因子β1（TGF-β1）分泌很可能是其中的重要发病机制之一。     

From mitochondria to disease: role of the renin-angiotensin system

Mitochondria are energy-producing organelles that conduct other key cellular tasks. Thus, mitochondrial damage may impair various aspects of tissue functioning. Mitochondria generate oxygen- and nitrogen-derived oxidants, being themselves major oxidation targets. Dysfunctional mitochondria seem to contribute to the pathophysiology of hypertension, cardiac failure, the metabolic syndrome, obesity, diabetes mellitus, renal disease, atherosclerosis, and aging. Mitochondrial proteins and metabolic intermediates participate in various cellular processes, apart from their well-known roles in energy metabolism. This emphasizes the participation of dysfunctional mitochondria in disease, notwithstanding that most evidences supporting this concept come from animal and cultured-cell studies. Mitochondrial oxidant production is altered by several factors related to vascular pathophysiology. Among these, angiotensin-II stimulates mitochondrial oxidant release leading to energy metabolism depression. By lowering mitochondrial oxidant production, angiotensin-II inhibition enhances energy production and protects mitochondrial structure. This seems to be one of the mechanisms underlying the benefits of angiotensin-II inhibition in hypertension, diabetes, and aging rodent models. If some of these findings can be reproduced in humans, they would provide a new perspective on the implications that RAS-blockade can offer as a therapeutic strategy. This review intends to present available information pointing to mitochondria as targets for therapeutic Ang-II blockade in human renal and CV disease.     

The renin-angiotensin system and progression of kidney disease

CONSTRICTIVE ACTIVITY OF THE RAS AND DEVELOPMENT OF RENAL DISEASES: Several studies have suggested that the constitutive level of activity of the renin-angiotensin system (RAS), and especially of angiotensin converting enzyme (ACE) which plays an important role in the kidney in determining intrarenal angiotensin and kinin concentrations, is genetically determined and linked to the risk of developing several vascular diseases, including diabetic nephropathy, and to the risk of renal function deterioration in glomerular diseases of several origins. INHIBITION OF THE RAS AND PROGRESSION OF RENAL DISEASES: Large controlled clinical trials have shown over the past years that inhibition of ACE has a beneficial effect and protects against degradation of renal function in type I diabetes with microalbuminuria and also in renal diseases of several origins. PATHOPHYSIOLOGY: All these observations taken together suggest that activation of the RAS, which is necessary in certain circumstances to maintain glomerular filtration and tissue perfusion, can have a long-term deleterious effect on the heart, vessels, and kidneys, especially through glomerular hypertension which can lead to glomerulosclerosis. They support the use of ACE inhibitors, within the indications deduced from analyses of the large clinical trials, for protecting renal function in kidney diseases.     

The renin-angiotensin system and hypertension in autosomal recessive polycystic kidney disease

Hypertension is a well-recognized complication of autosomal recessive polycystic kidney disease (ARPKD). The renin-angiotensin system (RAS) is a key regulator of blood pressure; however, data on the RAS in ARPKD are limited and conflicting, showing both up- and down-regulation. In the current study, we characterized intrarenal and systemic RAS activation in relationship to hypertension and progressive cystic kidney disease in the ARPKD orthologous polycystic kidney (PCK) rat. Clinical and histological measures of kidney disease, kidney RAS gene expression by quantitative real-time PCR, angiotensin II (Ang II) immunohistochemistry, and systemic Ang I and II levels were assessed in 2-, 4-, and 6-month-old cystic PCK and age-matched normal rats. PCK rats developed hypertension and progressive cystic kidney disease without significant worsening of renal function or relative kidney size. Intrarenal renin, ACE and Ang II expression was increased significantly in cystic kidneys; angiotensinogen and Ang II Type I receptor were unchanged. Systemic Ang I and II levels did not differ. This study demonstrates that intrarenal, but not systemic, RAS activation is a prominent feature of ARPKD. These findings help reconcile previous conflicting reports and suggest that intrarenal renin and ACE gene upregulation may represent a novel mechanism for hypertension development or exacerbation in ARPKD.     

The renin-angiotensin system in transgenic rats

Transgenic animals are used to study the function, regulation and in vivo expression of genes. The effects of the genes of the renin-angiotension system on blood pressure regulation and hypertension were investigated in transgenic rats. The role of the renin-angiotensin system in the development of cardiovascular hypertrophy of hypertensive renal damage was analysed, as well as its interaction with other hormonal systems, i.e. adrenal steroids. The development of a transgenic rat strain carrying the mouse REN-2 gene has provided a new model of hypertension with systolic blood pressure values of 200 mmHg. This model is characterised by low active plasma renin, hyperproreninaemia and high expression of renin in the adrenal gland and other extrarenal tissues. Transgenic rats with thehuman components of the renin-angiotensin system expressed the human renin and angiotensinogen proteins which interacted species-specifically in transgenic rats. These transgenic models demonstrate the feasibility of studying the function of candidate hypertension genes in transgenic animals. In the future, further refinements in transgene construction, mutation, and modification can be tested in such transgenic animal models.     

肾素-血管紧张素系统阻断剂的肾保护作用

近年来大量研究揭示，体内肾素血管紧张素系统（RAS）过度激活在肾脏病慢性进展中发挥了十分重要的作用。以血管紧张素转换酶抑制剂（ACEI）和血管紧张素Ⅱ受体拮抗剂（ARB）为代表的RAS阻断剂通过降低血压、减少蛋白尿、抑制肾脏纤维化和延缓肾功能进展而发挥肾脏保护作用，已得到越来越多的临床和实验证实。但是随着对RAS研究的深入，RAS阻断剂临床应用中仍存在不少理论和实践问题，我们着重对其中最常见的10个问题，结合最新研究文献进行解答。     

Genetic polymorphisms of the renin-angiotensin system in end-stage renal disease.

BACKGROUND: End-stage renal disease (ESRD) is a complex phenotype resulting from underlying kidney diseases of different etiologies as well as from environmental and genetic factors. The responsible genes influencing the development and rate of progression to ESRD have yet to be defined. We examined an association of the three renin-angiotensin system (RAS) gene polymorphisms with renal disease and progression to ESRD in dialyzed patients. METHODS: Genotyping was performed in 745 ESRD patients and 520 control subjects for the angiotensin-converting enzyme (ACE) I/D, angiotensinogen (AGT) M235T and angiotensin II type 1 receptor (AT1R) A1166C gene polymorphisms using polymerase chain reaction and gel analysis. RESULTS: Allele and genotype frequencies of the ACE polymorphism did not differ significantly between ESRD patients and controls. The patient group showed an increased frequency of the T allele of the AGT polymorphism (P = 0.02) and the C allele and CC genotype of the AT1R polymorphism (P<0.01). There was an association of the AT1R gene polymorphism with the progression of renal disease to end-stage failure. The time from diagnosis to the onset of ESRD was significantly shorter in patients carrying the C allele than in subjects with the homozygous AA genotype (4.7 years vs 12.6 years, P<0.001). The observed effect was not associated with hypertension in studied subjects. CONCLUSION: The results of our study demonstrate the association between the AT1R A/C polymorphism and renal disease progression. The CC/AC genotype of this polymorphism might serve as a predictor for early ESRD and might be useful in planning therapeutic strategies for individual patients.