非对称二甲基精氨酸在肾脏疾病及其心血管并发症中的作用

非对称二甲基精氨酸(asymmetric dimethyl arginine,ADMA)是内源性一氧化氮合酶(nitric oxide synthesis,NOS)的竞争性抑制剂,可引起内皮功能损伤.研究发现ADMA 作为一种重要的尿素症毒素,在患者的肾功能下降及其心血管并发症中发挥重要作用.药物及肾替代治疗对其在体内的清除尚有待进一步的研究.研究ADMA在肾脏疾病中的作用,有助于提高慢性肾脏病患者的预后.     

非对称性二甲基精氨酸与高血压、急性冠脉综合征的相关性研究

目的 检测高血压、急性冠脉综合症（Acutecoronarysyndrome,ACS）患者中血浆非对称性二甲基精氨酸（Asymnlet．ricdimethylarginine,ADMA）、一氧化氮舍酶（nitriooxidesynthase,NOS）和一氧化氮（nitricoxide,NO）的水平,观察其水平变化与高血压、ACS之间的相关性,探讨ADMA在高血压、ACS发生发展中所起的作用。方法将符合条件的91例患者作为研究对象分成2组,其中单纯性高血压组（HP组）60例,急性冠脉综合征组（ACS组）31例,正常对照组60例,比较各组的ADMA、NO、NOS的浓度,分析它们在高血压、ACS的变化。结果高血压组、ACS组血浆ADMA水平均高于对照组,ACS组ADMA水平最高,各组比较均有统计学差异,血浆ADMA水平与NOS、NO水平分别呈负相关。结论ADMA在高血压、ACS的发生发展中发挥了一定作用,ADMA水平与血管内皮功能障碍密切相关,检测ADMA水平有望成为评价高血压、ACS病情严重程度的新指标和新方法,并对指导治疗可能具有一定的临床价值。     

盐敏感性高血压患者药物治疗选择

将我院2010年12月～2012年12月通过急性盐水负荷试验所筛查出来的180例盐敏感性高血压患者作为研究对象,利用随机数字法将其均分为观察组与对照组,对照组患者给予硝苯地平缓释片加依苏片治疗,观察组患者给予武力都治疗,所有患者在治疗前后均给予1次实验室以及ABPM检查,所有患者均进行了8w的治疗,对两组患者每天所需药品的平均费用进行比较。结果在治疗过程中,两组患者在舒张压以及收缩压（DBP/SPB）方面与治疗前相比,均有所下降;两组患者均无严重的不良反应;对照组患者的日平均药费为3.513元,观察组为0.725元,两组患者的日平均药费以及给药前后舒张压、收缩压存在较大的差异,具有统计学意义,P〈0.05。在对盐敏感性高血压患者进行药物治疗时,武力都具有较高的性价比。     

住院高血压患者对盐敏感性及健康教育需求的调查

目的了解住院高血压患者对盐敏感性的认知程度及健康教育需求。方法采用自行设计的问卷对90例住院高血压患者进行调查,并根据调查结果进行分析。结果住院高血压患者普遍缺乏盐敏感性知识,93．33％的患者不知道盐敏感性高血压;96．67％的患者不知道盐敏感性高血压的预防方法;35．56％的患者愿意接受限制高盐饮食;超过50％的患者希望得到各种形式的健康教育;71．11％的患者选择了护士作为施教者。结论医务人员宜实施多种形式的健康教育,采取以护士为主医生选择性参与的健康教育模式。     

老年高血压患者盐敏感性认知的调查

目的探讨老年高血压患者对盐敏感性相关知识的认知情况。方法采用自行设计的调查问卷对120例老年高血压患者进行盐敏感性相关知识的问卷调查,并对结果进行分析。结果95.83%的患者不了解盐敏感性的相关知识;73.33%的患者未接受限盐饮食治疗;患者均有该问题健康教育的需求,且所有患者均喜欢一对一的教育方式。结论老年高血压患者对盐敏感性相关知识的认知较差,对低盐饮食的接受和关注度较低。护理人员应采用合适的教育方法,有针对性地实施健康教育,以预防和降低盐敏感性高血压的发生。     

高血压病患者盐敏感性判定的意义及护理配合

高血压病是一种遗传与环境因素相互作用所致的疾病,盐是重要的环境因素之一.盐敏感性高血压指高盐摄入引起的血压显著升高,而限制盐摄入可使升高的血压下降.     

盐敏感性高血压的诊断和机制

原发性高血压是由遗传与环境因素长期相互作用所致的疾病,而盐是其中重要的易患因素之一。不同种族和个体间对盐负荷或限盐呈现出不同的血压反应,即存在盐敏感性问题。盐敏感性的定义20世纪70年代末,Luft等[1]和Kawasaki等[2]分别采用急性和慢性盐负荷试验对正常受试者进行     

高血压患者血清尿酸与ADMA的关系

目的:研究原发性高血压患者血清尿酸与非对称性二甲基精氨酸(asymmetric dimethylarginine;ADMA)的关系.方法:检测原发性高血压合并高尿酸血症患者内皮系统ADMA 水平,并与单纯高血压组作对比,了解高尿酸对高血压患者内皮系统功能的影响,探讨高血压患者血清尿酸与内皮ADMA的关系.结果:高血压合并高尿酸血症组病人的血清ADMA水平高于单纯高血压组病人(P＜0.05);高血压病人的血清尿酸水平与ADMA呈正相关关系,r=0.713;P＜0.001;高血压患者ADMA与尿酸水平的多因素回归分析,尿酸是唯一有统计学意义的影响ADMA水平的自变量,其回归系数为0.002,P＜0.001.结论:本研究提示高血压患者血清尿酸水平与内皮ADMA呈正相关关系,高尿酸血症患者血清ADMA水平升高.     

可溶性生长刺激表达基因2蛋白联合非对称二甲基精氨酸对哮喘急性发作风险的预测价值

目的 探讨可溶性生长刺激表达基因2蛋白(sST2)与非对称性二甲基精氨酸(ADMA)联合应用在支气管哮喘(哮喘)患者急性发作预测中的价值。方法 本研究为前瞻性研究,于2018年1月至2020年10月对在北京大学深圳医院诊断为哮喘的病例进行电话随访,记录其3个月内有无急性发作的发生。将有哮喘急性发作者分入风险组,无急性发作者分入稳定组。比较两组基线资料的均衡性;将可能影响哮喘急性发作的参数纳入单因素分析;将单因素分析中有意义的指标纳入多因素Cox回归模型,获取对哮喘急性发作有预测价值的指标;使用受试者工作特征曲线(ROC)分析各指标单独及联合检测对哮喘急性发作的预测价值。结果 共纳入哮喘患者194例,21例急性发作,173例患者在3月内未出现急性发作。多因素Cox回归显示,高sST2水平(HR=1.107,95%CI:1.057～1.160,P<0.01)及高ADMA水平(HR=1.076, 95%CI:1.020～1.135,P<0.01)为预测哮喘急性发作的独立预测因子。ROC曲线分析显示,sST2(截断值为18.0 ng/ml)及ADMA(截断值为0.54μmol/L)...     

原发性高血压患者血浆ADMA浓度外周循环内皮祖细胞数量的变化

目的探讨原发性高血压（EH）患者血浆非对称性二甲基精氨酸（ADMA）浓度、外周循环内皮祖细胞（EPCs）数量的变化及两者之间的关系。方法选取停止服用降压药至少2周以上并排除冠状动脉粥样硬化性心脏病、糖尿病的原发性高血压患者46例,对照组25例为健康体检者。采用反相高效液相色谱法（RP—HPLC）测定血浆ADMA含量,流式细胞术分析外周循环EPCs。结果EH组血浆ADMA浓度[（0.363±0．029）μg/ml]显著高于对照组[（0．319±0．022）μg／ml]（P〈0．01）。EH组外周循环EPCs数量[（0．368±0．121）％]显著低于对照组[（0．588±0．139）％]（P〈0．01）。血浆ADMA浓度与外周循环EPCs数量呈负相关关系（r=-0．706,P〈0．01）。结论EH患者血浆ADMA浓度升高,外周循环EPCs数量减少,两者之间呈负相关关系。EH患者循环EPCs数量下降部分原因可能是由于血浆ADMA水平升高所致。     

Increased asymmetric dimethylarginine and nitric oxide levels in patients with migraine

Asymmetric dimethylarginine (ADMA) has been found as correlated with endothelial dysfunction and oxidative stress. There are few studies regarding ADMA and nitric oxide (NO) levels in patients with migraine and alterations of ADMA and NO levels during migraine attack are not well-known. Therefore, in present study, we aimed to measure NO and ADMA levels in patients with migraine and compare them with the control group to investigate the correlation between migraine, oxidative stress and endothelial dysfunction. The migraine group consisted of 59 patients, including 22 suffering from migraine with aura and 37 suffering from migraine without aura. The control group consisted of 31 healthy volunteers without headache. The patients in migraine group were divided into subgroups based on whether attack period was present or not and whether it was migraine with or without aura. Plasma ADMA levels were measured using an enzyme-linked immunosorbent assay method. Migraine patients had higher concentrations of NO (35.6±7.7, 31.0±6.2 μmol/L, respectively, p=0.005) and ADMA (0.409±0.028, 0.381±0.044 μmol/L, respectively, p = 0.001) levels when compared with the healthy controls. During migraine attack, NO and ADMA levels were found to be significantly higher in migraine group as compared to control group (respectively, p=0.015, p=0.014). Similarly, NO and ADMA levels in the patients with migraine in the interictal period were found to be significantly higher as compared to control group (p=0.011, p=0.003). In conclusion, higher ADMA and NO levels of patients with migraine supported that oxidative stress and endothelial dysfunction may have a role in migraine pathogenesis.     

Hyperhomocysteinaemia is not associated with increased levels of asymmetric dimethylarginine in patients with ischaemic heart disease

BACKGROUND: Elevated plasma total homocysteine appears to be related to endothelial dysfunction and impaired nitric oxide production. We aimed to investigate [1] whether elevated levels of plasma total homocysteine are associated with high plasma levels of asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase, and [2] whether reduction of plasma total homocysteine levels by folate and vitamin B supplementation lowers plasma concentration of asymmetric dimethylarginine. MATERIALS AND METHODS: Sixty patients with ischaemic heart disease and with plasma total homocysteine levels of 15.0 micromol L-1 were randomized to open therapy with folic acid, pyridoxine and cyancobalamin for 3 months (n = 30) or to no treatment (n = 30). Samples were also obtained from 34 patients with plasma total homocysteine levels of 8.0 micromol L-1 on admission. RESULTS: Plasma asymmetric dimethylarginine concentrations in patients with elevated total homocysteine levels were not significantly higher (0.68 +/- 0.19 micromol L-1) than in patients with low total homocysteine levels (0.61 +/- 0.10 micromol L-1; P = 0.08). Plasma asymmetric dimethylarginine level in the vitamin supplemented group was 0.65 +/- 0.12 micromol L-1 before, and 0.64 +/- 0.12 micromol L-1 after 3 months of vitamin supplementation (NS). Plasma asymmetric dimethylarginine levels were correlated with serum cystatin C levels (P < 0.001). CONCLUSION: A nonsignificant trend to increased plasma levels of asymmetric dimethylarginine in patients with high plasma total homocysteine levels may be explained by concomitant subtle renal dysfunction. Substantial reduction of plasma total homocysteine did not affect the level of plasma asymmetric dimethylarginine.     

血液透析患者肺动脉高压与血管内皮功能紊乱的相关性

目的 研究维持性血液透析（maintenance hemodialysis,MHD）患者肺动脉高压（pulmonary hypertension,PAH）与内皮细胞功能紊乱之间的关系.方法 选取维持性血液透析患者60名,行心脏彩超检查,以肺动脉收缩压（PASP）≥35mmHg的为肺动脉高压组（PAH组）,PASP＜35 mmHg的为无肺动脉高压组（无PAH组）,分别收集2组患者临床资料和实验室数据,在透析间期测量2组患者血流介导的肱动脉内皮依赖性舒张功能（FMD）及人血不对称二甲基精氨酸（ADMA）浓度.结果 60例患者17人存在PAH（28.3％）,PAH组和无PAH组患者透析间期体质量增加量与干体质量比值及高敏C反应蛋白（hs-CRP）存在显著差异（P＜0.05）.经检测PAH组和无PAH组FMD分别为（12.2±1.3）％和（6.9±1.2）％,ADMA分别为（2.97±0.31）μmol/L和（2.i0±0.29）μmol/L,采用协方差分析法矫正可能和血管内皮功能相关的其他因素后,得出FMD和ADMA在两组之间均有显著差异（F=63.8,P＜0.001,F=16.832,P＜0.01）.二分类Logistic回归分析显示,左心室质量分数（LVMI） （B=0.037,P=0.043）和ADMA （B=9.519,P=0.006）是MHD患者并发PAH的主要相关因素.结论 MHD合并PAH的患者存在显著的血管内皮细胞功能紊乱,LVMI和人血ADMA是MHD患者并发PAH的主要相关因素.     

ADMA损伤血管内皮后Apelin-13对大鼠血压的影响

目的探讨在非对称性二甲基精氨酸(ADMA)导致大鼠血管内皮损伤的病理条件下,血管活性肽apelin-13对大鼠离体血管产生的效应及对血压的影响。方法成年雄性SD大鼠20只,分为ADMA组和对照组。用微量渗透泵给予两组大鼠分别持续注射ADMA[10 mg/(kg.d)]和生理盐水,28天。基线水平测量大鼠血压。28天后复测血压并检测血清ADMA、一氧化氮(NO)的浓度。给予大鼠尾静脉注射apelin-13(10 nmol/kg),观察血压变化。使用透射电镜观察大鼠尾动脉血管内皮细胞超微结构。行离体尾动脉实验观察apelin-13(10-10～10-5 mol/L)对两组血管环的作用。结果 28天后,ADMA组大鼠血清ADMA浓度明显高于对照组,而NO浓度降低。ADMA组大鼠收缩压较对照组明显升高(154±5 mmHg比123±4 mmHg,P<0.01)。静脉注射apelin-13(10 nmol/kg)后,ADMA组大鼠血压升至159±3 mmHg(P<0.05),而对照组降至113±3 mmHg(P<0.05)。透射电镜下可观察到ADMA组大鼠血管内皮细胞出现变性甚至坏死。离体血管实验表明apelin-13使ADMA组血管收缩而诱发对照组血管环舒张,呈浓度依赖性。结论 ADMA可对血管内皮细胞造成严重损伤,并导致大鼠高血压。在这种病理状态下,apelin-13可促进血管收缩,进而加重大鼠高血压。     

血清不对称二甲基精氨酸与服用质子泵抑制剂后初次发生急性冠状动脉综合征的相关性

目的本研究旨在探讨血清不对称二甲基精氨酸（ADMA）与服用质子泵抑制剂（PPI）后初次发生急性冠状动脉综合征（ACS）的关系。 方法研究纳入2017年1月至2018年10月因初次发生ACS入住徐州医科大学附属淮安医院的患者及体检中心同期健康体检者共210例,分为3组,PPI组（服用PPI＋初次发生ACS）患者70例,其中男性51例,女性19例,平均年龄为（62.80±11.87）岁;ACS组（未服用PPI＋初次发生ACS）患者70例,其中男性55例,女性15例,平均年龄为（62.66±12.13）岁;对照组为同期健康体检患者（未服用PPI＋未发生ACS）70人,其中男性54人,女性16人,平均年龄为（62.96±9.09）岁。采用酶联免疫吸附法检测血清ADMA浓度,同时测量总胆固醇、三酰甘油等指标。采用单因素方差分析、非参数检验和χ²检验比较3组研究对象一般人口学信息、各项生化指标及ADMA水平;组间两两比较采用Mann-Whitney U检验;采用Spearman相关分析分析血清ADMA水平与ACS传统危险因素的关系;采用多因素Logistic回归分析探讨ACS的独立危险因素。 结果PPI组和ACS组的血清ADMA水平均高于对照组,差异均有统计学意义（Z=-9.585、-4.793,P均<0.001）;PPI组的血清ADMA水平高于ACS组,差异具有统计学意义（Z=-8.750,P<0.001）;PPI组和ACS组（即ACS患者）的血清ADMA水平与年龄、性别、BMI、吸烟、糖尿病、高血压、总胆固醇、三酰甘油无相关性（P均>0.05）;Logistic回归分析显示血清ADMA水平是初发ACS患者的独立危险因素（β=0.017,OR=1.017,P<0.001）。 结论服用PPI后初次发生ACS患者的血清ADMA水平明显高于未服用PPI的初次发生ACS患者;初次发生ACS患者的血清ADMA水平明显高于健康对照者;血清ADMA升高是初次发生ACS的独立危险因素。     

血液透析对ADMA的清除作用及与NO生成的相关性研究

目的观察血液透析对尿毒症患者体内非对称性二甲基精氨酸（asymmetic dimethyl arginine,ADMA）的清除作用及与一氧化氮（nitricoxide,NO）生成的相关关系。方法选择单中心维持性血液透析（maintenance hemodialysis,MHD）患者159例,检测透析前、后血清ADMA和一氧化氮代谢产物（nitricoxide productions,NOx）的浓度,测算单次透析清除ADMA和NOx的总量,对比MHD患者透析前后、MHD患者与健康对照、MHD患者不同年龄组、糖尿病与非糖尿病组、高血压、低血压与血压稳定组之间透析前血清ADMA及NOx的浓度,对透析前和透析后血清ADMA与NOx浓度分别进行相关性分析。结果MHD患者透析后血清ADMA水平明显降低[（1.05±0.67）μmol/L比（0.83±0.53）μmol/L,P〈0.001],NOx水平明显升高[（61.1±38.5）μmol/L比（96.1±58.1）μmol/L,P〈0.001];4h血液透析对ADMA和NOx的总清除量为[（9.15±4.70）μmol和（448.62±58.59）μmol];与健康人相比,MHD患者透析前后ADMA水平都高[（1.05±0.67）μmol/L、（0.83±0.53）μmol/L比（0.35±0.06）μmol/L,P值分别为0.002和0.004],NOx水平则相当[（61.1±38.5）μmol/L、（96.1±58.1）μmol/L比（68.1±13.6）μmol/L,P值分别为0.596和0.166];MHD患者各组之间透析前血清ADMA与NOx水平差异均无统计学意义;透析前、后ADMA与NOx水平均呈明显负相关关系（r分别为-0.344和-0.612,P值分别为0.047和0.001）。结论MHD患者透析前血清ADMA水平高于健康人,NOx水平与健康人相当;血液透析可以清除ADMA和NOx,对ADMA的清除作用相对要小;透析后血清NOx水平升高可能与透析清除ADMA等抑制NO生成的物质有关。     

Dysregulation of dimethylargininedimethylaminohydrolase/asymmetric dimethylarginine pathway in rat type II diabetic nephropathy

An impaired generation of nitric oxide has been associated with diabetic renal disease. In order to elucidate the underlying molecular mechanisms into how nitric oxide synthesis is impaired in diabetic renal disease, we examined changes in activities and expressions of some renal enzymes involved in nitric oxide production during the development of diabetic nephropathy in type II diabetic Otsuka Long-Evans Tokushima Fatty rats. Ten-week old Otsuka Long-Evans Tokushima Fatty (n = 40) and control Long-Evans Tokushima Otsuka rats (n = 20) were given drinking water containing 20% sucrose to accelerate the development of diabetic nephropathy. Otsuka Long-Evans Tokushima Fatty rats developed diabetic nephropathy in an age-dependent manner. Renal nitric oxide synthase activities in Otsuka Long-Evans Tokushima Fatty rats gradually declined with the progression of diabetic mellitus and were significantly lower than those of age-matched Long-Evans Tokushima Otsuka rats after 22 weeks of age. The lower activities of renal nitric oxide synthase in Otsuka Long-Evans Tokushima Fatty rats were correlated with relatively higher levels of renal free asymmetric dimethylarginine, an endogenous nitric oxide synthase inhibitor, and were also correlated with decreased activities of dimethylargininedimethylaminohydrolase which metabolizes asymmetric dimethylarginine to citrulline. These results imply that dimethylargininedimethylaminohydrolase dysregulation may play an important role in the development of diabetic nephropathy by increasing asymmetric dimethylarginine levels, which leads to inhibition of renal nitric oxide synthesis.     

Serum asymmetric dimethylarginine and nitric oxide levels in obese postmenopausal women

Background: It has been reported that estrogen deficiency after menopause might cause a decrement in nitric oxide (NO) bioavailability by increasing the level of asymmetric dimethylarginine (ADMA), a major endogenous nitric oxide synthase inhibitor, thus leading to abnormalities in endothelial function. Because NO plays an important role on feeding behavior, ADMA may be involved in the pathogenesis of obesity, too. This cross‐sectional study aimed to evaluate the relations of ADMA and NO with the obesity‐linked peptides, such as ghrelin, leptin, and adiponectin in postmenopausal women free of hormone replacement therapy. Methods: Adiponectin, ghrelin, leptin, ADMA, and NO_x (total nitrite/nitrate) were measured in 22 obese (BMI: 30–47 kg/m²) and 19 normal weight (BMI: 21.5–26 kg/m²) postmenopausal women.Anthropometric measurements (height, weight, BMI, waist, and hip circumferences) were recorded. Statistics were made by the Mann–Whitney U‐test. Results: Ghrelin and adiponectin levels were significantly lower (P<0.001), whereas ADMA and leptin levels were higher in obese women than in normal weight controls (P<0.01 and 0.001, respectively). BMI was correlated negatively with adiponectin and ghrelin and positively with ADMA and leptin levels. No correlation existed between ADMA and NO. Conclusion: Estrogen deficiency alone may not cause an increase in ADMA levels unless the women are prone to disturbances in energy homeostasis. In spite of the high ADMA levels, the unaltered NO levels in plasma may be owing to ongoing inflammatory conditions. J. Clin. Lab. Anal. 25:174–178, 2011. © 2011 Wiley‐Liss, Inc.