氨基脲敏感性胺氧化酶及其病理生理意义

氨基脲敏感性胺氧化酶是一类对氨基脲敏感的胺氧化酶,功能复杂、分布广泛,其催化的氧化脱氨反应与心血管疾病和糖尿病血管并发症等关系密切,如氨基脲敏感性胺氧化酶催化的氧化脱氨反应参与了内皮细胞介导的低密度脂蛋白氧化,从而引起内皮损伤,最终导致动脉粥样硬化。氨基脲敏感性胺氧化酶可以调节葡萄糖转运蛋白4从脂肪细胞或3T3F422A细胞的胞内转位至胞膜,进而摄取并转运葡萄糖。其代谢物甲胺和甲醛等有血管毒性,特别在糖尿病并发症的发生发展中具有不可忽视的作用。     

氨基胍抑制氨基脲敏感性胺氧化酶活性对糖尿病大鼠血管并发症的预防作用

目的探讨氨基胍在体内外对氨基脲敏感性胺氧化酶（SSAO）的抑制效果及对糖尿病大鼠血管并发症的预防作用。方法取雄性SD大鼠主动脉匀浆作为SSAO酶样来源,体外应用苯甲胺作为SSAO催化底物,在酶促反应体系中加入一系列浓度的氨基胍,采用高效液相色谱法检测SSAO活性;取雄性SD大鼠35只,随机分为正常对照组、糖尿病模型组（DM组）和氨基胍干预组（DM＋氨基胍组）,采用单次腹腔注射链脲佐菌素建立糖尿病模型,DM＋氨基胍组腹腔注射氨基胍25mg/（kg·d）。8周末检测大鼠血浆SSAO活性、甲胺、甲醛、内皮素1（ET-1）、一氧化氮（NO）浓度,同时检测主动脉组织SSAO活性,HE染色及透射电镜分别观察大鼠胸主动脉、肾组织形态学改变。结果氨基胍对大鼠主动脉组织SSAO具有较强的抑制作用,IC₅₀为12.47μmol/L;DM组SSAO活性、ET-1浓度高于正常对照组,血浆NO浓度低于正常对照组（P<0.01）;氨基胍明显抑制糖尿病大鼠SSAO活性,降低ET-1浓度,升高甲胺、NO浓度（P<0.01）;DM＋氨基胍组主动脉、肾组织病理改变较DM组明显减轻。结论氨基胍可有效抑制SSAO活性,可通过抑制SSAO氧化脱氨作用预防糖尿病血管并发症。     

氨基脲敏感性胺氧化酶的结构与功能

氨基脲敏感性胺氧化酶（Semicarbazide—sensitive amine oxidase．SSAO）是一组含铜和锟并对氨基脲敏感的多功能酶，广泛存在于哺乳动物体内脉管含量丰富的组织中，它影响内源性和外源性芳香族和脂肪族一元胺的代谢。SSAO主要以两种形式存在，一种是可溶性的形式，主要存在于循环血液中；一种是膜结合的形式，主要存在于脂肪细胞、     

急性心肌梗死患者血浆单胺氧化酶活性与血清心肌肌钙蛋白水平的关系

研究证实单胺氧化酶( MAO)是心肌活性氧(ROS)的主要来源,并且,MAO生成的ROS能分别触发不同信号路径导致细胞增殖、肥大或凋亡,因此,MAO在心血管疾病中,如心衰及缺血再灌注损伤,具有重要作用[1].研究提示血浆中MAO活性变化能很好地反映急性心肌梗死(AMI)发生和严重程度,由于其容易测量的特性,使其可能成为新的心肌梗死标识物[2].心肌肌钙蛋白(cTn)Ⅰ对诊断AMI具有高度敏感及高度特异性,cTn Ⅰ浓度可作为判断AMI时梗死范围的指标,可反映心肌器质性改变[3].本研究通过分析AMI时血浆MAO活性与血清cTn Ⅰ水平相关性,从而以心肌器质损害程度的角度提出血浆MAO能反映心肌梗死严重程度的依据.     

急性心肌梗死患者血浆单胺氧化酶活性检测及临床意义

单胺氧化酶(MAO)为含黄素类的单胺类氧化酶,存在于细胞的线粒体外膜上,催化单胺类物质被氧化脱氨,生成过氧化氢、氨和相应醛。血浆MAO升高,主要发生于肝脏纤维化、肢端肥大症。最近,MAO在心血管疾病中的作用逐步得到     

冠心病合并高血压患者血浆内皮素1水平与冠脉病变程度的关系

经冠状动脉造影（CAG）确诊为冠心病患者238例,分为冠心病合并高血压154例（A组）,单纯冠心病84例（B组）;另选择健康对照组50例（C组）。测定各组生化指标及内皮素1（ET-1）水平并观察患者CAG病变情况。结果A、B组血脂及ET．1水平显著高于C组（P〈0．05,〈0．01）。A组与B组比较,ET-1水平显著高于B组（P〈0．01）;且A组冠状动脉单支病变、多支病变者ET-1水平均高于B组（P均〈0．01）,A、B两组中多支病变者ET-1水平较单支病变者显著增高（P〈0．01,〈0．05）。认为冠心病合并高血压患者ET-1水平与冠状动脉病变程度密切相关。     

吲达帕胺治疗盐敏感性高血压效果的研究

目的比较吲达帕胺与氢氯噻嗪在治疗盐敏感性高血压中疗效的差异。方法收集我院初始开始药物的轻中度高血压患者120例,通过盐负荷试验分为盐敏感组（SS组）及非盐敏感组（NSS组）,每组再随机分为两个亚组,分别给予氢氯噻嗪25mg及吲达帕胺2.5mg治疗12周,比较治疗前后血压及动态血压。结果 SS组中吲达帕胺治疗后患者收缩压及舒张压较NSS组下降更为明显（P〈0.05）,NSS组中两组间无显著差异（P〉0.05）;动态血压检测表明,SS组中吲达帕胺治疗组患者白天、夜间及24小时收缩压及舒张压的下降幅度显著高于氢氯噻嗪组（P〈0.05）,而NSS组中两治疗亚组间的下降幅度无显著差异（P〉0.05）。结论吲达帕胺较氢氯噻嗪更能够有效降低盐敏感性高血压患者的血压。     

老年高血压和冠心病患者的高胰岛素血症

目的探讨老年原发性高血压和冠心病患者的血胰岛素水平及胰岛素敏感性指数的变化。方法对无糖尿病病史的老年原发性高血压患者３０例、老年冠心病患者３２例、老年对照组３０例测定空腹及餐后２小时血糖、胰岛素、Ｃ肽值,计算胰岛素敏感性指数,进行对照分析。结果空腹胰岛素,高血压组为（１３．１±５．４）ｍＵ／Ｌ,冠心病组为（１１．１±０．３）ｍＵ／Ｌ,对照组为（１０．３±１．９）ｍＵ／Ｌ;餐后２小时胰岛素,３组分别为（６２．３±１６．８）、（４４．３±６．４）及（１０．８±３．１）ｍＵ／Ｌ。均为高血压组高于冠心病组,二者又高于对照组（分别为Ｐ＜０．０５及Ｐ＜０．０１）。胰岛素敏感性指数为对照组大于冠心病组,二者又大于高血压组（分别为Ｐ＜０．０１及Ｐ＜０．０５）。结论老年高血压患者及冠心病患者均伴有高胰岛素血症和胰岛素抵抗,胰岛素敏感性指数降低是血管病变的危险因素之一。     

单胺氧化酶基因A和B的二种多态与高血压的关系

目的：探讨单胺氧化酶（ＭＡＯ）基因多态性与高血压发病的关系。　　方法：按世界卫生组织标准收集高血压患者１０４例为高血压组,正常对照组１０１名。利用聚合酶链式反应（ＰＣＲ）和凝胶电泳技术对所有个体进行ＭＡＯ基因多态性分析,所检测的基因包括ＭＡＯ－Ａ的一个限制性片段长度多态（ＲＦＬＰ）和ＭＡＯ－Ｂ的一个二核苷酸重复多态（ＤＮＲＰ）。采用统计学方法探讨ＭＡＯ基因多态性与高血压发病的关系。　　结果：ＭＡＯ－Ａ 基因对于内切酶ＥｃｏＲＶ 的２ 个ＲＦＬＰ等位基因在高血压组和正常对照组的分布无显著差异;ＭＡＯ－Ｂ基因所表现的７种ＤＮＲＰ等位基因中,１９５ ｂｐ 和１９９ ｂｐ 片段在高血压组和正常对照组中表现出显著差异（χ２检验,Ｐ＜ ０．０５）。　　结论：ＭＡＯ－Ｂ基因多态可能影响高血压发病,其机制需进一步研究。     

Aminoguanidine inhibits semicarbazide-sensitive amine oxidase activity: implications for advanced glycation and diabetic complications

Summary Aminoguanidine, a nucleophilic hydrazine, has been shown to be capable of blocking the formation of advanced glycation end products. It reduces the development of atherosclerotic plaques and prevents experimental diabetic nephropathy. We have found that aminoguanidine is also quite potent at inhibiting semicarbazide-sensitive amine oxidase (SSAO) both in vitro and in vivo. The inhibition is irreversible. This enzyme catalyses the deamination of methylamine and aminoacetone, which leads to the production of cytotoxic formaldehyde and methylglyoxal, respectively. Serum SSAO activity was reported to be increased in diabetic patients and positively correlated with the amount of plasma glycated haemoglobin. Increased SSAO has also been demonstrated in diabetic animal models. Urinary excretion of methylamine is substantially increased in the rats following acute or chronic treatment with aminoguanidine. Urinary methylamine levels were substantially increased in streptozotocin (STZ)-induced diabetic rats following administration of aminoguanidine. The non-hydrazine SSAO inhibitor (E)-2-(4-fluoro-phenethyl)-3-fluoroallylamine hydrochloride (MDL-72974A) has been shown to reduce urinary excretion of lactate dehydrogenase (an indicator of nephropathy) in STZ-induced diabetic rats. Formaldehyde not only induces protein crosslinking, but also enhances the advanced glycation of proteins in vitro. The results support the hypothesis that increased SSAO-mediated deamination may be involved in structural modification of proteins and contribute to advanced glycation in diabetes. The clinical implications for the use of aminoguanidine to prevent glycoxidation have been discussed. [Diabetologia (1997) 40: 1243–1250] Received: 8 May 1997 and in revised form: 24 June 1997     

Elevated plasma semicarbazide-sensitive amine oxidase (SSAO) activity in Type 2 diabetes mellitus complicated by retinopathy.

AIMS: To measure plasma semicarbazide-sensitive amine oxidase (SSAO) activities and detect retinopathy in Type 2 diabetes mellitus (DM). METHODS: Cross-sectional, population-based study of 65 diabetes patients (61 diagnosed from the age of 30 years) with or without retinopathy as determined by fundus photography in primary care. HbA1c was analysed by ion exchange chromatography on a Mono S for HbA1c column. SSAO activities were assayed radiometrically and formaldehyde-albumin adducts by ELISA in plasma samples from patients and 136 healthy controls. RESULTS: Subjects with diabetes had higher plasma SSAO activity, measured as nmol benzylamine x mlplasma(-11) x h(-1)(mean 20.6), than controls (mean 14.3), P<0.0001; 95% confidence interval (CI) for difference 4.9-7.7. SSAO activity was higher in patients with retinopathy (mean 23.2) than in those without (mean 18.9), P=0.012; 95% CI for difference 1.0-7.5, and related to the HbA1c value. No statistically significant relationship between diabetes duration and SSAO activity was found. With HbA1c values and insulin treatment entered into a multiple logistic regression model, SSAO activity no longer predicted retinopathy, P increasing from 0.025 to 0.17. SSAO activity and the presence of any retinopathy were unrelated to titres of antibodies against formaldehyde-treated human serum albumin. CONCLUSIONS: SSAO activity, earlier found to be elevated in Type 1 DM, is also elevated in Type 2 DM. The SSAO family of enzymes may be involved in the development of diabetic retinopathy, possibly by catalysing the formation of toxic metabolites. A potent and specific inhibitor of human SSAO might help prevent retinopathy in Type 1 and Type 2 DM.     

Circulating semicarbazide-sensitive amine oxidase is raised both in Type I (insulin-dependent), in Type II (non-insulin-dependent) diabetes mellitus and even in childhood Type I diabetes at first clinical diagnosis

Summary Plasma semicarbazide-sensitive amine oxidase is raised in patients with Type I (insulin-dependent) diabetes mellitus. It has been suggested that this enzyme is involved in the development of microvascular damage through its ability to convert amines (e. g. methylamine and aminoacetone) into aldehydes, hydrogen peroxide and ammonia. Plasma semicarbazide-sensitive amine oxidase was found to be equally raised both in patients with Type I diabetes (n = 73) and Type II (non-insulin-dependent) diabetes mellitus (n = 88) compared with control subjects (621 ± 209 and 619 ± 202 vs 352 ± 102 mU/l, p < 0.0001) and to correlate in multiple regression analysis with HbA_{1 c}. Since the enzyme could protect the islets from the inhibitory effects of methylamine on insulin secretion, we also tested sera of 100 children, collected consecutively at first diagnosis of Type I diabetes, for semicarbazide-sensitive amine oxidase. The activity was greatly increased compared with serum values of 76 control (siblings) children (757 ± 300 vs 455 ± 138 mU/l, p < 0.0001), but not associated with HbA_{1 c}. Our study confirms the increase of plasma semicarbazide-sensitive amine oxidase in Type I diabetes and extends this finding to Type II diabetes as well as to childhood Type I at first clinical diagnosis. In the last case increased enzyme activities could serve to protect the islets from inhibitory effects of methylamine but cause damage by generation of hydrogen peroxide, aldehydes and ammonia. In the long run the increased enzyme activities could also contribute to vascular damage by direct cytotoxic action on endothelial cells, including increased oxidative stress and glycosylation of proteins. [Diabetologia (1999) 42: 233–237] Received: 22 December 1997 and in revised form: 3 August 1998     

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治疗高血压的主要目标是最大程度地降低长期心血管发病和死亡的总危险。多数临床研究显示,血压控制达标需要多种药物联合治疗才能达到。同时高血压合并冠心病患者仅仅降压是不够的,综合管理冠心病患者的多重心血管危险因素是十分重要的,除降压达标外,血脂、糖尿病、吸烟等危险因素的管理同样不可忽视。同时所有患者在服药的基础上,都要进行适当的生活方式调整,包括限盐、戒烟、限制饮酒、饮食调整、适度运动、控制体重等。     

Clinical characteristics and outcomes of Chinese patients with coronary heart disease and resistant hypertension

There is currently few research on clinical characteristics and outcomes of coronary heart disease (CHD) with resistant hypertension in central region of China. This study aimed to assess the risk factors and outcomes of CHD and resistant hypertension in population of central region of China. A total of 1467 CHD patients with hypertension were included and considered to three groups according to blood pressure control: controlled group (blood pressure < 140/90 mmHg on three or less antihypertensive drugs); uncontrolled group (blood pressure ≥ 140/90 mmHg on two or less antihypertensive drugs); or resistant group (blood pressure ≥ 140/90 mmHg on three antihypertensive drugs or < 140/90 mmHg on at least four antihypertensive drugs including diuretic). The authors evaluated the clinical outcomes of three groups at 1-year follow-up. The prevalence of resistant hypertension was 21.8%. Significant adjusted associated factors of resistant hypertension included per unit changes body mass index (BMI, OR 1.12), and four categorical variable diagnosis by yes or no: heart failure (HF, OR 2.62), left ventricular hypertrophy (LVH, OR 2.83), diabetes (OR 1.55), and chronic kidney disease (CKD, OR 1.63). In multiple adjusted Cox regression analysis, patients in resistant group had a higher risk of the primary outcome (HR, 2.14 [95% CI, 1.47–3.11]; p < .001). Moreover, the risk of atherosclerotic cardiovascular disease (ASCVD) in patients with resistant hypertension is also significantly increased (HR, 2.11 [95% CI, 1.39–3.20]; p < .001). In conclusion, resistant hypertension was a quite common and high proportion finding in patients with CHD and hypertension in central region of China, and these patients have a worse clinical prognosis.     

老年高血压病并发冠心病心率变异性分析

目的 :探讨老年高血压病并发冠心病患者的自主神经活动特点。方法 :　对 5 9例原发性高血压 （EH）、5 4例冠心病 （CHD）和 38例 EH并发 CHD患者与 34例健康老年人的心率变异性 （HRV）进行对比研究。结果 :EH组和CHD组与对照组除 EH组的 R- R间期标准差的平均数 （SDNNIndex）外 ,其余参数差异均有显著性 （P<0 .0 5 ） ;EH并发 CHD组与对照组比较 ,参数差异均有非常显著意义 （P<0 .0 1） ;但不同疾病组间比较 ,差异均无显著性 （P>0 .0 5 ）。结论 :高血压病和冠心病患者的自主神经功能受损 ,当高血压病并发冠心病时这种受损更加明显。其迷走神经张力降低 ,交感神经紧张性相对增高是导致老年患者心率变异性降低的主要原因。     

中国冠心病二级预防研究——老年高血压人群的干预结果分析

目的探讨血脂康对合并高血压的老年患者和无高血压史的老年患者冠心病二级预防结果。方法对一项随机、双盲、安慰剂对照试验中的1 530例合并高血压的老年患者(治疗组772例,对照组758例)和1 020例无高血压史的老年患者(治疗组508例,对照组512例)平均服用血脂康胶囊4年后的冠心病二级预防结果进行统计分析。结果与无高血压史的老年患者比较,合并高血压的老年患者的冠心病事件发生率增加38.1%(P=0.0097),脑卒中事件发生率增加156.3%(P=0.0003),总死亡率增加48.2%(P=0.0035)。在合并高血压的老年患者中,治疗组与对照组比较,冠心病事件减少38.2%(P=0.0009);总死亡事件减少36.3%(P=0.0030);新发肿瘤事件减少49.2%(P=0.0395),其中肿瘤死亡减少67.1%(P=0.0123)。在无高血压史的老年患者中,治疗组与对照组比较,冠心病事件减少47.8%(P=0.0025),其中冠心病死亡减少43.7%(P=0.0369);对经皮冠状动脉介入治疗和(或)冠状动脉旁路移植术的需求减少71.3%(P=0.0018);总死亡事件减少32.0%(P=0.0936)。两类老年患者中均没有发现治疗组临床不良事件或实验室安全指标的增加。结论合并高血压的老年冠心病患者较无高血压史的老年患者处于更高危状态,血脂康胶囊用于老年患者的冠心病二级预防是安全有效的。     

高浓度血浆血小板衍生生长因子C对冠心病患者冠状动脉病变的影响

目的探究血浆血小板衍生生长因子C(PDGF-C)浓度变化与冠心病及冠状动脉病变程度的关系。方法选择行冠状动脉造影住院的急性冠状动脉综合征(ACS)患者52例、稳定型心绞痛(SAP)患者52例,以及造影结果正常的其他患者为对照组50例。冠心病(ACS和SAP)患者中冠状动脉多支病变者60例,双支病变者25例,单支病变者19例。酶联免疫吸附试验(ELISA)法测定各组患者血浆PDGF-C浓度。比较各组间血浆PDGF-C浓度水平,并进行Spearman相关性分析、Logistic回归分析及绘制ROC曲线。结果 ACS组及SAP组血浆PDGF-C浓度比对照组高(P0.05)。冠状动脉多支及双支病变组血浆PDGF-C浓度比单支病变组高(P0.05)。Spearman相关性分析发现,血浆PDGF-C浓度与Gensini评分有一定相关性(r=0.218,P0.05)。Logistic回归分析发现,高浓度血浆PDGF-C相比于低浓度血浆PDGF-C,患者发生冠心病的风险增加(OR=1.006, 95%CI 1.002～1.011)。血浆PDGF-C浓度的ROC曲线下面积为0.645,灵敏度为77.88%。结论高浓度血浆PDGF-C可能是冠心病发病的危险因素,与冠状动脉病变的严重程度可能存在一定的关联。     

微小RNA对老年冠心病慢性心力衰竭合并高血压的影响

目的探讨微小RNA对老年冠心病慢性心力衰竭(CHF)合并高血压的影响。方法连续收集2017年1月~2019年1月于我院收治的原发性高血压患者520例,根据患者是否合并CHF,分为CHF组178例和对照组342例,观察2组患者微小RNA谱(微小RNA-1、-21、-23、-29、-30、-130、-133、-195、-199、-208和-320)表达的差异,用Pearson相关性分析,用多因素logistic回归分析影响因素。结果与对照组比较,CHF组患者收缩压和舒张压明显增高[(166.85±12.75)mm Hg vs(158.74±13.71)mm Hg(1 mm Hg=0.133 kPa),P=0.000、(105.73±14.83)mm Hg vs(98.47±10.75)mm Hg,P=0.000];LVEF明显降低[(41.74±5.75)%vs(57.85±6.02)%,P=0.000];且CHF组微小RNA-1、微小RNA-21、微小RNA-23、微小RNA-29、微小RNA-130、微小RNA-195、微小RNA-199相对表达量增加(P<0.05)。2组微小RNA-30、微小RNA-133、微小RNA-208、微小RNA-320相对表达量比较,均无统计学差异(P>0.05)。微小RNA-1、微小RNA-21、微小RNA-23、微小RNA-29、微小RNA-130、微小RNA-195、微小RNA-199相对表达量与LVEF呈显著负相关(P<0.01)。多因素logistics回归分析显示,微小RNA-1、微小RNA-21、微小RNA-23、微小RNA-29、微小RNA-130、微小RNA-195、微小RNA-199相对表达量增加是CHF的影响因素(P<0.05,P<0.01)。结论微小RNA-1、微小RNA-21、微小RNA-23、微小RNA-29、微小RNA-130、微小RNA-195、微小RNA-199表达量增加可能与冠心病的老年患者并发CHF有关。     

血浆结合珠蛋白浓度与早发冠心病的关系研究

目的检测早发冠心病（PCHD）患者血浆结合珠蛋白（Hp）水平,观察不同类型早发冠心病患者血浆珠蛋白水平。方法纳入2010年5月～2011年1月PCHD患者72例,同期纳入健康体检者74例作为对照组。将PCHD组依诊断进一步分为稳定性心绞痛组（SA,n=15）、不稳定性心绞痛组（UA,n=36）和急性心肌梗死组（AMI,n=21）;检测并比较各组Hp浓度的差异。结果 PCHD组Hp浓度高于对照组,差异有统计学意义[（1.785±0.525）ng/mLvs.（0.869±0.172）ng/mL,P〈0.05];SA组、UA组和AMI组Hp浓度分别为（1.699±0.723）ng/mL、（1.685±0.453）ng/mL和（1.946±0.584）ng/mL,组间比较无明显差异（P=0.281）。结论 PCHD患者血浆Hp浓度明显升高,且与类型无关。