Changes in angiotensin converting enzyme activity in the renal vascular bed of streptozotocin-induced diabetic rat

The purpose of this study was to look for evidence of changes in angiotensin converting enzyme activity in the renal vascular bed of streptozotocin (STZ)-induced diabetic rats. To assess the activity of the enzyme, we examined angiotensin I- and angiotensin II-induced vasoconstriction in perfused kidneys from controls and diabetic rats. Angiotensin I (3x10(-9) to 3x10(-6) M) induced a dose-dependent vasoconstriction in control kidneys; this response was completely inhibited by losartan (10(-5) M) and markedly inhibited by both captopril (10(-4) M) and indomethacin (10(-5) M). Angiotensin II (10(-10) to 3x10(-7) M) also caused a dose-dependent vasoconstriction in control kidneys; this response was markedly enhanced by 10(-4) M L-NNA, and significantly inhibited by losartan (10(-5) M). Angiotensin I-induced vasoconstriction was slightly greater in STZ-induced diabetic rats than in controls, but the maximal response was unaffected. These results suggest that angiotensin I is rapidly converted to angiotensin II in the renal vascular bed, and that converting enzyme activity in the renal vascular bed may be decreased in STZ-induced diabetic rats.     

金属硫蛋白在大鼠缺血预处理中的变化

目的：探讨大鼠心脏缺血预处理（IPC）中金属硫蛋白（MT）的变化。方法：采用经典的IPC模型，与I/R心肌损伤比较。实验动物分为3组：假手术组（n=6），开胸旷置2 h 20 min；缺血/再灌注组（n=12），结扎左冠状动脉前降支40 min，再灌注1 h 40 min；经典IPC组（n=12），按经典的Murry法复制。以心肌MT的含量，心肌梗塞范围，心肌组织丙二醛（MDA）含量和超氧化物歧化酶（SOD）活性为观察指标。结果：IPC组心肌MT含量明显高于I/R组（P<0.01），心肌MDA含量明显低于I/R组（P<0.01），心肌SOD活性明显高于I/R组（P<0.01）。经直线相关分析，IPC组心肌MT含量与SOD活性呈正相关（r=0.91, P<0.01），与MDA含量呈负相关（r=-0.92, P<0.01），IPC组心肌梗塞范围明显小于I/R组（P<0.05）。结论：缺血预处理能促进大鼠心肌MT合成，MT可能参与IPC的保护效应。     

非创伤性预处理在离体心脏抗再灌注损伤中作用机制的探讨

目的:观察非创伤性肢体缺血预处理对大鼠离体再灌注心肌是否有保护作用。方法:实验采用体重(250±30)gSD雄性大鼠25只随机分成3组,在Langendorff装置上对大鼠离体心脏进行灌流。对照组(C,n=8):在灌注全程均用富氧K-H液(充以95%O₂+5%CO₂),在恒压(8.33kPa)、恒温(37℃)条件下灌注;缺氧/复氧组(A,n=8):预灌15min后,灌注心脏先全心缺血缺氧15min,随后15min复氧再灌注(37℃);非创伤性肢体缺血预处理组(N-WIP,n=9):先将大鼠双后肢捆绑5min,松开5min,反复4次后,随后的方法同R组。在相应时点分别测定冠脉流出液和心肌匀浆中超氧化物歧化酶(SOD)活性,Ca²⁺-Mg²⁺-ATP酶活性和丙二醛(MDA)含量,同时记录心肌细胞的单相动作电位(MAP)和心肌收缩张力曲线。结果:非创伤性肢体缺血预处理能使再灌注心律失常发生率显著低于A组;心肌组织中MDA含量显著低于A组,心肌组织中SOD活性显著高于A组,心肌细胞的膜电位、Ca²⁺-Mg²⁺-ATP酶活性及肌张力较稳定。结论:非创伤性肢体缺血预处理对大鼠离体再灌注心肌有明显的保护作用,可能是通过增强心肌的抗氧化能力、稳定心肌Ca²⁺-Mg²⁺-ATP酶活性和膜相结构等途径,提高心肌细胞对再灌注损伤的抵抗力。     

Serum angiotensin converting enzyme in pneumonias.

Serum concentrations of angiotensin converting enzyme (ACE) were studied in pneumonias caused by different pathogens and in cases in which the aetiology could not be defined. In all aetiological groups, except in viral pneumonia, there was a significant increase in ACE during recovery (p less than 0.001). In several patients the lowest values during the acute phase of disease and the highest values during recovery were outside the reference limits. In cases with known aetiology the highest ACE values and the difference between the lowest and the highest values correlated positively with C-reactive protein concentrations at admission (p less than 0.001). The pathophysiology behind the fluctuations of the ACE concentrations is unknown.     

细胞外信号调节的蛋白激酶对糖尿病大鼠心肌缺血预处理的影响

目的：观察缺血预处理（IPC）对糖尿病大鼠心脏缺血/再灌注心律失常和心功能的影响以及与心肌细胞外信号调节的蛋白激酶1/2(ERK1/2)的关系。方法： 利用四氧嘧啶复制糖尿病大鼠模型。8周后，采用冠脉结扎及放松的方法复制心肌IPC及缺血再灌注模型 。动物分为非糖尿病IPC组（A组）、非糖尿病非IPC组（B组）、糖尿病IPC（C组）及糖尿病非IPC组（D组）。观察标准肢体导联（Ⅱ）心电图、左心室发展压（LVDP）、收缩期和舒张期左心室内压的最大变化速率（±dp/dtmax%）及心肌磷酸化细胞外信号调节的蛋白激酶1/2(ERK1/2)表达。结果： （1）A组心律失常评分显著低于B组和C组（均P<0.01），而其余各组间均无显著差异（均P>0.05）。（2）A组LVDP值和+dp/dtmax %明显高于B组和C组（均P<0.01），而其余各组间均无显著差异；-dp/dtmax% A组显著高于B组（P<0.01），而其余各组间均无显著差异（均P>0.05）。（3）A组心肌ERK1/2磷酸化表达明显高于B组和C组，而C组与D组比较没有明显差异。结论： IPC可以减轻非糖尿病大鼠缺血再灌注心律失常的严重程度，改善心功能，而在糖尿病大鼠中，这种保护作用并不明显。ERK1/2激活可能是IPC心肌保护作用的产生机制之一；糖尿病大鼠IPC保护作用减弱可能与其不能明显激活ERK1/2有关。     

Serum angiotensin converting enzyme in diabetic retinopathy.

Serum levels of angiotensin converting enzyme (SACE) were measured in 118 diabetic patients divided into the following four groups: 44 insulin-treated diabetic patients with severe retinopathy, 38 non insulin-treated diabetic patients with severe retinopathy, 18 diabetic patients, including both insulin-treated and non insulin-treated subjects with background retinopathy, 18 diabetic patients, insulin-treated and non insulin-treated without signs of retinopathy. Nineteen retinopathic patients non diabetic were also studied in order to verify whether SACE levels are altered when retinopathy is present independently from diabetes. The control group was composed of 44 normal subjects. When the data from the above six groups of subjects were submitted to statistical tests (one-way ANOVA, T-test of Bonferroni and test of Student-Newman-Keuls), the study yielded the following results: i) a remarkable difference between the SACE levels in healthy subjects and those in the three groups of diabetic retinopathic patients considered; ii) a non statistically significant difference of SACE levels between normal subjects and diabetic patients without retinopathy; iii) a non statistically significant comparison of SACE levels of normal subjects versus non diabetic retinopathic patients. Therefore, we concluded that while primitive diseases of the retina are not associated with an increase of SACE levels, yet when diabetes and retinopathy coexist, the SACE levels increase remarkably (in rather an independent way from the type of diabetes, the age of subjects, the stage of retinal disease and the daily average insulin dose), suggesting that most of the enzyme's increase originates from the endothelium of peripheral vasa, widely involved in most of the retinopathic diabetic patients.     

Lysozyme and angiotensin converting enzyme levels in experimental mycobacterial granulomas

A study has been made on mycobacterial-induced granulomas in guinea-pig lymph nodes. Lysozyme and angiotensin-converting enzyme (ACE) were measured in the auricular lymph nodes and serum of guinea-pigs which had received live BCG (Pasteur) or Cobalt (Co)-irradiated armadillo-derived Mycobacterium leprae intradermally into the ear or dinitrofluorobenzene (DNFB) painted epicutaneously upon the ears. In the lymph nodes with granulomas induced by either live BCG or killed M. leprae, the mean concentrations of lysozyme and ACE varied directly with the mean weight of the lymph nodes but the temporal pattern of weight change differed with the two agents. In M. leprae recipients at the time of peak lymph node weight, serum lysozyme and ACE values were significantly greater than those observed in controls; in animals receiving live BCG (Pasteur), serum lysozyme but not ACE values were elevated significantly at the time of peak lymph node weight. Four days following the epicutaneous application of DNFB, where there was no granuloma, there was a similar increase in the concentration of lysozyme and ACE in the lymph nodes. At the same time, there was also significant elevation in the serum lysozyme and ACE concentrations. Thus, in the granulomatous responses, the parallel tissue and serum changes in lysozyme and ACE concentrations were consistent with increased production and secretion of each enzyme by cells of the mononuclear phagocyte series. The increased lysozyme and ACE concentrations found in the lymph nodes of DNFB sensitised animals gives further evidence that such changes are not unique to granulomas. Finally, the intradermal administration of dead M. leprae in guinea pigs also produced increased lysozyme and ACE levels similar to that found in leprosy in man.     

Serum angiotensin converting enzyme level in bronchial asthma.

Using hippuryl-L-histidyl-L-leucine as a substrate analogue, serum angiotensin converting enzyme (ACE) was spectrophotometrically estimated in patients with bronchial asthma. The mean level of asthmatic patients was significantly lower than that of the control subjects. The reduced serum ACE activities did not change during an acute asthmatic attack. Significantly lower levels of serum ACE occurred in patients with chronic asthma than in those who only suffered with occasional asthma. Serum ACE activity was not reduced when the patients were taking steroids. Serum ACE activity could not be correlated with either the systolic blood pressure or the diastolic blood pressure of our asthmatic patients. However, serum ACE activity was correlated with the serum beta-globulin fraction in asthmatic patients.     

血管紧张素转换酶2与心血管疾病研究进展

血管紧张素转换酶2(ACE2)是SARS病毒(SARS-CoV)、新型冠状病毒(SARS-CoV-2)感染机体的主要受体,也是肾素-血管紧张素-醛固酮系统的主要成员之一。ACE2对多种心血管疾病具有保护作用,SARS-CoV-2可以降低机体ACE2的表达,这可能是新型冠状病毒肺炎(COVID-19)后期产生心血管并发症的原因之一。本文总结了ACE2在多种心血管疾病发病过程中的作用及其机制,希望为新型冠状病毒肺炎(COVID-19)的治疗提供新的思路。     

Cortical alterations of angiotensin converting enzyme, angiotensin II and AT1 receptor in Alzheimer's dementia.

We investigated the immunohistochemical alterations of angiotensin converting enzyme (ACE), angiotensin II and AT1 receptor in the parietal cortex in Alzheimer's dementia (AD) to reveal the contributive role of the brain renin-angiotensin system in the disease process. In controls, ACE, angiotensin II and AT1 immunoreactivities were localized to pyramidal neurons of the cortex. The staining intensity was distinctly increased in AD for all three antigens, involving predominantly cortical layer V, which may reflect the enhanced brain renin-angiotensin system activity in the disease process. In addition, a prominent perivascular ACE and angiotensin II immunoreactivity surrounding some cortical vessels in aged controls and AD patients points to an underlying microvascular pathology in the process of neurodegeneration.     

心麻痹液有助于缺血预处理幼兔的心肌保护作用

缺血预处理(ischemic preconditioning,IPC)是一个在许多种动物上都观察到的内源性心肌保护现象。一些研究认为ATP敏感性钾通道(KATP channel)开放可能与IPC产生心肌保护的机制有关。鉴于高钾浓度的心麻痹液是临床上最为常用的心肌保护措施之一,但细胞外高浓度钾是否会影响到KATP通道开放?因此,本研究利用Langendorff离体心脏灌注模型研究IPC单独应用和与心麻痹液(St．Thomas Ⅱ号停搏液)联合应用对兔未成熟心脏全心缺血再灌注的影响,以了解心麻痹液在IPC心肌保护效应中的作用。     

血管紧张素转换酶2研究进展

肾素-血管紧张素系统(renin-angiotensin sys-em,RAS)是一个非常古老而复杂的调节系统,低等生物如酵母菌即有完整的RAS。在哺乳类动物,RAS不仅对水盐代谢、维持血压稳定起重要作用,而且还是心血管、泌尿、生殖等系统发育和功能调节的一个重要系统;在炎症反应、损伤的修复、愈合及造血等病理生理过程中亦起重要作用。血管紧张素转换酶(angiotensin convertingenzyme,ACE)是血管紧张素合成主要的限速酶,是RAS的枢纽。随研究的不断深入,发现RAS的复杂程度远远超出人们的想象,尽管对它的研究已超过了100年,但对RAS的认识才刚刚开始。20…     

西藏藏族人群血管紧张素转换酶基因多态性分布

目的:探讨西藏拉萨、那曲地区藏族健康人群血管紧张素转换酶(ACE)基因第16内含子287bpAlu顺序插入/缺失(I/D)多态性分布。方法:采用聚合酶链反应(PCR)方法检测ACE基因型。结果:76例拉萨藏族人ACE基因型频率分别为Ⅱ=0．395,ID=0．316,DD=0．289,等位基因频率分别为Ⅰ=0．553,D=0．447。81例那曲藏族人ACE基因型频率分别为Ⅱ=0．346,ID=0．444,DD=0．210,等位基因频率分别为Ⅰ=0．568,D=0．432。结论:拉萨、那曲地区藏族人ACE基因型及等位基因频率分布无显著差异;西藏藏族与英国白人和美国黑人相比基因型及等位基因频率均存在显著性差异,但与韩国人及日本人相似。     

Characteristics, assay and semeiologic value of angiotensin converting enzyme (ACE)

Serum angiotensin conversion enzyme (serum ACE) is a dipeptidylcarboxypeptidase which activates angiotensin I to angiotensin II and inactivates bradykinine. It is a glycoprotein with an MW of 126,000 to 480,000. It is produced by all endothelial cells, and is located on the cell membrane. It is inhibited by EDTA (chelator of Zn-- cofactor), teprotide (snake venom nonapeptide) and captopril. Estimation of ACE has greatly benefitted from the use of synthetic tripeptides. An example is the method of Cushman and Cheung using hippuryl histidyl leucine. A raised serum ACE level in sarcoidosis has been demonstrated by Liebermann in 1975. The diagnostic value is limited by the existence of high levels in other pulmonary diseases (asbestosis, silicosis). Serum ACE levels in sarcoidosis are all higher when the disease is diffuse from a pulmonary and extrapulmonary standpoint. They decrease when the disease regresses spontaneously and rise if it worsens. Radiological improvement in pulmonary sarcoid lesions under the influence of corticosteroid therapy is accompanied by a fall in serum ACE levels. Persistence of this normalization as the dose is decreased is a favourable sign, whilst the reappearance of a high serum level may either reflect simple and isolated biological "rebound" or may accompany a recurrence of signs of the disease. Serum ACE measurement is thus an important factor in the surveillance of cases of treated sarcoidosis when the dose of corticosteroids is to be reduced.