血管紧张素转化酶相关羧肽酶和糖尿病肾病

血管紧张素转换酶（angiotensin—converting enzyme，ACE）是肾素-血管紧张素系统（RAS）的关键酶，能水解血管紧张素Ⅰ（ATⅠ）产生血管紧张素Ⅱ（ATⅡ），后者已证实是引起糖尿病肾组织损伤的核心环节之一。近年来一种与ACE高度同源的ACE相关羧肽酶（ACE—related carboxypeptidase，ACE2）正引起国外一些学者的关注，本文将就这一新近发现的酶及其在糖尿病肾病发病机制中的作用作介绍。     

血管紧张素转换酶抑制剂对早期糖尿病性肾病的防治作用

为探讨血管紧张素转换酶抑制剂（ＡＣＥＩ）对早期糖尿病性肾病的长期治疗作用，将４６例新诊断的血压正常、２４小时尿白蛋白排泄＜３０ｍｇ的非胰岛素依赖型糖尿病（ＮＩＤＤＭ）患者随机分为两组。Ａ组服ＡＣＥＩ培哚普利（ｐｅｒｉｎｄｏｐｒｉｌ），２ｍｇ／ｄ，Ｂ组为对照组。对两组患者的收缩压、舒张压、平均血压、肾小球滤过率、肾有效血浆流量、滤过分数、尿白蛋白排泄率（ＵＡＥＲ）、胰岛素敏感指数（ＳＩ）及血脂进行为期约２年的观察。结果表明，Ａ组用ＡＣＥＩ治疗２年后，ＮＩＤＤＭ者肾小球高滤过状态得以改善（Ｐ＜０．０５），ＵＡＥＲ明显减少（Ｐ＜０．０５），ＳＩ降低，血压稳定；而非ＡＣＥＩ治疗的Ｂ组，肾功能指标有恶化趋势，并且血压明显增高，ＳＩ改善不明显。两组的血脂在治疗前后变化均不明显（Ｐ＞０．０５）。提示小剂量培哚普利长期治疗，对早期糖尿病性肾病具有保护其肾功能的作用，并可改善胰岛素抵抗，减少动脉粥样硬化的危险因素     

血管紧张素转换酶抑制剂治疗糖尿病肾病

本文介绍了血管紧张素转换酶抑制剂治疗糖尿病肾病的理论基础,临床应用、疗效及副作用等。     

血管紧张素转换酶抑制剂治疗糖尿病肾病研究进展

综述了血管紧张素转换酶抑制剂治疗糖尿病肾病的现状、可能的机理以及副作用。     

血管紧张素转换酶抑制剂防治糖尿病肾病的作用机制

肾素-血管紧张素系统激活在糖尿病肾病的发生发展中具有重要意义。体外、动物、临床前及临床试验均证实:血管紧张素转换酶抑制剂具有防治糖尿病肾病和多重保护肾脏的作用,但其机制还不完全清楚。本文重点就血管紧张素转换酶抑制剂防治糖尿病肾病机制的研究进展作一综述。     

血管紧张素转换酶抑制剂治疗糖尿病肾病进展

本文对血管紧张素转换酶抑制剂治疗糖尿病肾病的临床应用及其作用机理作一全面介绍,并与其他降压药的作用作了详尽的比较.     

血管紧张素转换酶抑制剂和血管紧张素受体阻滞剂联合治疗糖尿病肾病的临床研究

目的比较血管紧张素转换酶抑制剂（ACEI）和血管紧张素受体阻滞剂（ARB）单独及联合治疗糖尿病肾病（DN）的疗效。方法183例DN患者，随机分为三组，分别予贝那普利、洛沙坦或两药联合治疗12周。比较治疗前后血压、尿蛋白及血钾和血Cr等的变化。结果上述两药均能有效降低DN的血压和尿蛋白且作用相似；联合治疗的降尿蛋白作用更明显（P〈0．05），但二者的降压效果相似（P〉0．05）。治疗前后的血钾、血Cr和Ccr无明显变化（P〉0．05）。结论对于DiN患者，ACEI和ARB联合治疗与单药相比具有更强的降尿蛋白作用，且这种作用是通过独立于血压的机制实现的。     

血管紧张素转换酶抑制剂和钙拮抗剂治疗糖尿病肾病

合理选择降压药物对延缓糖尿病肾病的发展具有重要意义。近年来，血管紧张素转换酶抑制剂（ＡＣＥＩ）和钙拮抗剂（ＣＡＩ）是两类最常用药物。为此，综述近十几年来使用此两类药物治疗糖尿病肾病的疗效比较，观察蛋白尿、肾血流动力学等的改变，为临床治疗提供参考     

血管紧张素转换酶2与糖尿病肾病

The identification of angiotensin-converting enzyme (ACE)2 opened new recognition of renin-angiotensin system (RAS). ACE2 degrades Ang Ⅱ to Ang (1-7), maintains homeostasis of RAS with ACE. Studies have revealed that ACE2 has important functions in diabetic nephropathy. It may be a target for drug and is used as gene therapy for diabetic nephropathy. Amplifying ACE2 activity may have a potential therapeutic role for diabetic nephropathy.     

血管紧张素转换酶2与糖尿病肾病

The identification of angiotensin-converting enzyme (ACE)2 opened new recognition of renin-angiotensin system (RAS). ACE2 degrades Ang Ⅱ to Ang (1-7), maintains homeostasis of RAS with ACE. Studies have revealed that ACE2 has important functions in diabetic nephropathy. It may be a target for drug and is used as gene therapy for diabetic nephropathy. Amplifying ACE2 activity may have a potential therapeutic role for diabetic nephropathy.     

Preclinical studies on angiotensin converting enzyme inhibitors

Summary The identification of the renin-angiotensin-aldosterone system in the control of blood pressure, and the preclinical development of the angiotensin converting enzyme inhibitors for therapeutic use are reviewed. The properties of these compounds are discussed with respect to their in vitro enzyme inhibitory potency; prevention of the pharmacological effects of angiotensin I; potentiation of those of bradykinin; tissue enzyme inhibition; mechanism of effect on blood pressure both alone and in combination with other antihypertensive agents; and effect on cardiac parameters.     

钙拮抗剂与血管紧张素转换酶抑制剂对高血压靶器官的影响

目的探讨用钙拮抗剂（ＣａＡ）和血管紧张素转换酶抑制剂（ＡＣＥＩ）长期治疗对高血压病靶器官的影响。方法对３８６例高血压病Ｉ期或Ｉ期患者服用ＣａＡ或ＡＣＥＩ平均５．１±０．６年，按服药情况分为ＣａＡ组、ＡＣＥＩ组、对照组（间断服药）。结果长期服用ＣａＡ或ＡＣＥＩ不仅能使血压持续稳定在较低水平，而且随着血压的下降，左室肥厚逆转、心脏舒张功能改善、尿蛋白排泄量下降（Ｐ＜０．００１）、眼底病变好转（Ｐ＜０．０１），且无脑卒中发生（Ｐ＜０．０５～０．０１）；而对照组上述各项指标均较ＣａＡ组和ＡＣＥＩ组有加重趋势，其加重程度和观察时间呈正相关（Ｐ＜０．０１）。结论长期ＣａＡ或Ａ－ＣＥＩ治疗对高血压病患者的预后有益。     

Acute and long-term renal effects of angiotensin converting enzyme inhibition in normotensive, normoalbuminuric insulin-dependent diabetic patients

Glomerular filtration rate (GFR) (thalamate clearance), renal plasma flow (RPF) (hippuran clearance), and urinary albumin excretion rate (AER) were measured in 10 normoalbuminuric, normotensive insulin-dependent diabetic patients and 8 normal subjects before and during acute angiotensin converting enzyme (ACE) inhibition by means of enalapril (10 mg IV). The effect of placebo versus enalapril (30 mg day-1) was also studied for 3-month treatment periods in the insulin-dependent diabetic patients. Acute ACE-inhibition caused a decline in filtration fraction (FF) from 0.259 +/- 0.011 (+/- SE) to 0.237 +/- 0.013 (2p less than 0.01) in the diabetic patients, and from 0.210 +/- 0.010 to 0.188 +/- 0.006 (2p less than 0.02) in the normal subjects. Mean arterial blood pressure was lowered from 90 +/- 1 to 84 +/- 2 mmHg (2p less than 0.01) and from 91 +/- 1 to 86 +/- 2 mmHg (2p less than 0.05). No significant change in blood glucose, AER or fractional albumin excretion (theta Alb) was seen in either group. After 3 months of enalapril treatment FF was decreased from 0.253 +/- 0.011 to 0.235 +/- 0.011 (2p less than 0.05), AER from 5.6 x/ divided by 1.7 to 4.3 x/divided by 1.6 micrograms min-1 (2p less than 0.01) and theta Alb from 1.22 +/- 0.22 x 10(-6) to 0.92 +/- 0.12 x 10(-6) (2p less than 0.02). The decline in total renal resistance was not significant (0.175 +/- 0.013 to 0.165 +/- 0.012 mmHg ml-1 min-1) and significant changes in GFR, RPF, mean arterial pressure or HbA1c were not observed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Renal effects of angiotensin converting enzyme inhibitors: Nondiabetic chronic renal disease

Summary Based on studies in the rat remnant kidney model, it has been proposed that glomerular hypertension is responsible for the progressive nature of chronic renal disease. In that model, therapy with angiotensin converting enzyme (ACE) inhibitors reduced glomerular pressures. As a result, glomerular injury was reduced and the rate of progression of renal disease was slowed. Thus, alterations in hemodynamics may play an important role in glomerular injury. However, it is now evident that a variety of metabolic and other factors affect the progression of renal disease. Moreover, recent studies suggest that ACE inhibitors may also have beneficial effects that are independent of alterations in glomerular pressure. In humans, the glomerular hemodynamic response to renal disease cannot be measured, and it is not known whether or under which conditions glomerular capillary pressure might be elevated. Treatment with ACE inhibitors safely lowers blood pressure without adversely affecting renal function in mots patients with nondiabetic chronic renal failure. Although proteinuria and the rate of progression of renal disease may decrease in some patients, these effects are inconsistently seen. Identification of the factors that modulate this variability in response to ACE inhibition may provide new insight into the pathogenesis and treatment of progressive renal disease in humans.     

Comparison of the renal effects of angiotensin converting enzyme inhibitor and calcium antagonist in hypertensive Type 2 (non-insulin-dependent) diabetic patients with microalbuminuria: a randomised controlled trial

Summary Seven of eight hypertensive Type 2 (non-insulin-dependent) diabetic patients with microalbuminuria completed a randomised crossover trial to compare the renal effects of angiotensin converting enzyme inhibitor (enalapril) and calcium antagonist (nicardipine). Four-week fixed oral maintenance dosages of enalapril (10–20 mg/day) and nicardipine (60–120 mg/day) significantly (p<0.05) lowered the systolic and diastolic blood pressures without altering renal blood flow, glomerular filtration rate and filtration fraction. Both drugs significantly reduced (p<0.05) urinary albumin excretion rate and fractional clearance of albumin to similar extents. Total renal vascular resistance decreased significantly by nicardipine (p<0.05) and non-significantly by enalapril. Plasma osmotic pressure, plasma aldosterone concentration, total serum protein concentration, serum electrolytes and HbA_1c remained unchanged by these drugs, whereas plasma renin activity was significantly higher (p<0.05) in the enalapril than in the control and nicardipine phases. These results suggest that both drugs have similar renal function preserving effects with a concomitant hypotensive action in hypertensive Type 2 diabetic patients with microalbuminuria, and that the angiotensin converting enzyme inhibitor may not have advantageous renal effects when compared to the calcium antagonist and vice versa. Both drugs might be useful for treatment of high blood pressure in hypertensive diabetic patients, if long-term studies of these drugs can be shown to benefit the patients over other conventional antihypertensive therapies.     

血管紧张素转化酶抑制剂所致咳嗽与血管紧张素转化酶基因型相关性的研究

目的　探讨老年原发性高血压患者口服血管紧张素转换酶抑制剂 (ACEI )后发生咳嗽的机制。方法　应用聚合酶链反应 (PCR) ,检测老年原发性高血压患者口服ACEI后发生咳嗽与无咳嗽者的血管紧张素转化酶 (ACE)基因多态性 ,检测并比较两组患者血清ACE水平及ACE水平预测高血压患者口服ACEI引起咳嗽的敏感性和特异性。结果　ACEI所致咳嗽组ACE基因Ⅱ型的频率为4 0 % ,显著高于无咳嗽组 (2 0 % ,P <0 0 5 ) ,Ⅰ等位基因频率为 6 0 % ,显著高于无咳嗽组 (4 1% ,P <0 0 1)。两组患者血清ACE水平在DD型、ID型、Ⅱ型依次减低。咳嗽组血清ACE水平显著低于无咳嗽组 (P <0 0 0 1) ,血清ACE水平预测ACEI引起咳嗽的敏感性和特异性分别为 81%和 78%。结论　老年高血压患者口服ACEI所致咳嗽与血清ACE水平及ACE基因多态性有关。     

足细胞损伤对糖尿病肾病患者预后的影响

目的分析2型糖尿病肾病(DN)患者肾小球足细胞损伤特点、影响因素及其与肾功能远期预后的关系.方法回顾性分析经肾活检明确诊断并随访3年以上的24例2型DN患者的临床、病理资料.采用间接免疫荧光双标方法对肾活检组织分别进行足细胞标志物GLEPPl和Ⅳ型胶原α3链的双重染色,激光共聚焦显微镜采集图像,计算足细胞密度,并与临床、病理指标进行相关分析.详细记载随访过程中患者的实验室指标,根据Cockroft-Gault公式计算肌酐清除率(Ccr),对其进行线性回归分析,并据此分为肾功能稳定组(随访中Ccr保持稳定)和肾功能恶化组(随访中Ccr进行性减低).结果(1)DN患者足细胞密度较正常对照明显减少[(7.5±3.8%)vs(21.3±1.64%),P＜0.01].(2)肾活检时临床及病理资料相关分析显示,足细胞密度的减少与BMI、总胆固醇水平的增加有相关关系(r=-0.486,P＜0.05;r=-0.438,P＜0.05),长期血糖控制不佳者(糖化血红蛋白＞7%)足细胞密度减少的更为明显(P＜0.05).(3)足细胞密度与蛋白尿水平呈显著负相关,进一步多重回归分析显示,足细胞密度是蛋白尿增加的独立危险因素.此外,足细胞密度的减低还与肾小管功能损伤指标、肾小球硬化比例、间质纤维化的程度呈负相关(P＜0.05).(4)肾功能稳定组和肾功能恶化组比较分析显示,尽管长期随访中两组间血压、血糖、血脂水平均无明显差别(P＞0.05),但入组时两组间蛋白尿[(0.74±0.43)vs(3.51±1.17)g/24h,P＜0.01]和足细胞密度[(9.8±3.0)vs(6.5±3.8)%,P＜0.05]具有统计学差异.(5)长期随访,DN患者Ccr的斜率与足细胞密度有相关关系(r=0.424,P＜0.05).此外,糖尿病病程、蛋白尿、尿中大分子物质C3、α2-M均与Ccr的斜率相关(P＜0.05).结论糖尿病状态下,血流动力学异常,糖、脂代谢紊乱是足细胞损伤的重要相关因素.足细胞密度的减低与蛋白尿、小管功能损伤、肾组织慢性化病变等提示肾脏预后不良的因素相关.长期随访观察,足细胞损伤程度与DN肾功能预后密切相关;足细胞密度测定有助于DN患者病情轻重和预后的判断.     

维生素C对糖尿病肾病大鼠肾功能保护的作用机制

目的 探讨维生素C对糖尿病肾病（DN）大鼠肾功能的保护作用机制。方法 利用链脲佐菌素腹腔注射法诱导建立DN大鼠模型,将其随机分为维生素C治疗组（A组）、不用维生素C治疗组（B组）;并与正常对照组比较。观察治疗期间大鼠的一般状况、血糖、尿素氮（BUN）、血肌酐（SCr）、肾小球滤过率（GFR）、24h尿白蛋白排泄率（UAE）。结果 ①造模组大鼠均出现肾脏功能损害。②维生素C对血糖无影响,但能降低DN大鼠的BUN、SCr、24hUAE,增加GFR。结论 维生素C无糖作用,但有确切的肾脏功能保护作用。     

Angiotensin in cardiac surgery: efficacy in patients on angiotensin converting enzyme inhibitors

BACKGROUND: Patients presenting for cardiac surgery are often treated with angiotensin converting enzyme inhibitors (ACEIs), either for heart failure or hypertension. Control of systemic vascular resistance (SVR) during surgery can be difficult in such patients. Angiotensin II has been available as an unlicensed vasoconstrictor, but there is concern about renal damage and its use. AIM: This study compared a standard vasoconstrictor with angiotensin II and examined the effect on renal function after cardiac surgery. METHOD: Twenty consecutive, consenting patients scheduled for cardiac surgery that had been taking ACEIs for at least 6 months, were randomly assigned to receive either phenylephrine or angiotensin II for the control of SVR during and for 24 h after cardiac surgery. A pulmonary artery catheter was used to guide therapy. Creatinine clearance was measured before, 24 and 48 h after surgery. RESULTS: Low SVR and blood pressure requiring intervention was seen in all patients, particularly during cardiopulmonary bypass. One patient in the control group failed to respond to P, but responded normally to angiotensin II. Neither drug caused renal impairment. CONCLUSION: Angiotensin II is a safe alternative to phenylephrine in patients on ACEIs and should be considered in patients who fail to respond to conventional vasoconstrictors.