Asymmetric dimethylarginine, a biomarker of cardiovascular complications in diabetes mellitus

Cardiovascular(CV) complications are an essential causal element of prospect in diabetes mellitus(DM), with carotid atherosclerosis being a common risk factor for prospective crisis of coronary artery diseases and/or cerebral infarction in DM subjects. From another point of view, asymmetric dimethylarginine(ADMA) has been established as an inhibitor of endogenous nitric oxide synthesis and the relationship between ADMA and arteriosclerosis has been reported. In our study with 87 type 2 DM(T2DM) patients, we have examined whether ADMA and other CV risk factors are the useful predictors of DMCV complications. After the measurement of the respective CV risk factors, we have followed the enrolled T2 DM patients for 5 years. We have finally analyzed 77 patients. DMCV complications developed in 15 cases newly within 5 years, and 4 cases recurred. The concentrations of ADMA in plasma were markedly more elevated in 19 DM patients with CV complications than in 58 DM patients without CV complications. Urinary albumin(U-Alb), mean intimal-medial thickness(IMT) and ankle brachial index(ABI) were also higher in patients with CV complications. Multiple regression analyses showed that U-Alb had an influence on the high level of ADMA(standardized β = 6.59, P = 0.00014) independently of age, systolic BP, fibrinogen, mean IMT, plaque score, and ABI. The review indicates what is presently known regarding plasma ADMA that might be a new and meaningful biomarker of CV complications in DM subjects.

Liver plays a central role in asymmetric dimethylargininemediated organ injury

Asymmetric-dimethylarginine(ADMA) competes with L-arginine for each of the three isoforms of nitric oxide synthase:endothelial;neuronal;inducible.ADMA is synthesized by protein methyltransferases followed by proteolytic degradation.ADMA is metabolized to citrulline and dimethylamine,by dimethylarginine dimethylaminohydrolase(DDAH) and enters cells through cationic amino-acid transporters extensively expressed in the liver.The liver plays a crucial role in ADMA metabolism by DDAH-1 and,as has been recently demonstrated,it is also responsible for ADMA biliary excretion.A correlation has been demonstrated between plasma ADMA levels and the degree of hepatic dysfunction in patients suffering from liver diseases with varying aetiologies:plasma ADMA levels are increased in patients with liver cirrhosis,alcoholic hepatitis and acute liver failure.The mechanism by which liver dysfunction results in raised ADMA concentrations is probably due to impaired activity of DDAH due to severe inflammation,oxidative stress,and direct damage to DDAH.High plasma ADMA levels are also relevant as they are associated with the onset of multiorgan failure(MOF).Increased plasma concentration of ADMA was identified as an independent risk factor for MOF in critically-ill patients causing enhanced Intensive Care Unit mortality:a significant reduction in nitric oxide synthesis,leading to malperfusion in various organs,eventually culminating in multi organs dysfunction.

Effects of asymmetric dimethylarginine on renal arteries in portal hypertension and cirrhosis

AIM To evaluate the effects of asymmetric dimethylarginine(ADMA) in renal arteries from portal hypertensive and cirrhotic rats.METHODS Rat renal arteries from Sham(n = 15), pre-hepatic portal hypertension(PPVL; n = 15) and bile duct ligation and excision-induced cirrhosis(BDL; n = 15) were precontracted with norepinephrine, and additional contractions were induced with ADMA(10-6-10-3 mol/L), an endogenous inhibitor of nitric oxide(NO) synthase. Concentration-response curves to acetylcholine(1 × 10-9^(-3) × 10^(-6) mol/L) were determined in precontractedrenal artery segments with norepinephrine in the absence and in the presence of ADMA. Kidneys were collected to determine the protein expression and activity of dimethylarginine dimethylaminohydrolase(DDAH), an enzyme that catabolizes ADMA. RESULTS In renal arteries precontracted with norepinephrine, ADMA caused endothelium-dependent contractions. The pD 2 values to ADMA were similar in the Sham and PPVL groups(4.20 ± 0.08 and 4.11 ± 0.09, P > 0.05, respectively), but were lower than those of the BDL group(4.79 ± 0.16, P < 0.05). Acetylcholine-induced endothelium-dependent relaxation that did not differ, in terms of p D2 and maximal relaxation, among the 3 groups studied. Treatment with ADMA(3 × 10^(-4) mol/L) inhibited acetylcholine-induced relaxation in the 3 groups, but the inhibition was higher(P < 0.05) in the BDL group compared with that for the Sham and PPVL groups. The m RNA and protein expression of DDAH-1 were similar in kidneys from the three groups. Conversely, DDAH-2 expression was increased(P < 0.05) in PPVL and further enhanced(P < 0.05) in the BDL group. However, renal DDAH activity was significantly decreased in the BDL group. CONCLUSION Cirrhosis increased the inhibitory effect of ADMA on basal- and induced-release of NO in renal arteries, and decreased DDAH activity in the kidney.

Asymmetric dimethylarginine:A novel biomarker of gastric mucosal injury?

Nitric oxide(NO),a multifunctional endogenous gas molecule,is metabolized from L-arginine by enzymatic reaction in the presence of nitric oxide synthase.NO,an important gas signaling molecule,is a gastric mucosa protective factor that contributes significantly to maintain normal gastric mucosa integrity.NO increases gastric mucosa blood flow,regulates the secretion of mucus and bicarbonate,and inhibits the secretion of gastric juice.Asymmetric dimethylarginine(ADMA) has been identified as the major endogenous inhibitor of nitric oxide synthase.The function of ADMA is to decrease NO production via inhibiting nitric oxide synthase activity.Besides inhibiting NO synthesis,ADMA also directly induces oxidative stress and cell apoptosis,and participates in inflammation reaction.Its systemic accumulation was observed in conjunction with several cardiovascular and metabolic diseases.ADMA also mediates gastric ulcer injury induced by ethanol,stress,helicobacter pylori and indomethacin.The mechanism of ADMA directly producing adverse effect in gastric mucosa is incompletely understood.It is widely accepted that NO bioavailability decrease is the majority reason.Promotion of apoptosis and aggravation of inflammation may be other important mechanisms of ADMA-induced gastric injury.ADMA might be a novel clinical and experimental biomarker related to gastric mucosa disorder.Although therapeutic tool targeting to ADMA is available in multiple cardiovascular diseases,it is unknown in gastrointestinal disease.The strategy to inhibit ADMA is beneficial to gastric ulcer induced by ethanol in rats.Thus,ADMA might be a candidate of therapeutic target in gastric mucosa damage.

Transjugular intrahepatic portosystemic shunt-placement increases arginine/asymmetric dimethylarginine ratio in cirrhotic patients

AIM:To analyze the change of dimethylarginine plasma levels in cirrhotic patients receiving transjugular intrahepatic portosystemic shunt(TIPS).METHODS:To determine arginine,asymmetric dimethylarginine(ADMA),symmetric dimethylarginine(SDMA),and nitric oxide(NO) plasma levels,blood samples were collected from the superior cava,hepatic,and portal vein just before,directly after,and 3 mo after TIPS-placement.RESULTS:A significant increase in the arginine/ADMA ratio after TIPS placement was shown.Moreover,TIPS placement enhanced renal function and thereby decreased systemic SDMA levels.In patients with renal dysfunction before TIPS placement,both the arginine/ADMA ratio and creatinine clearance rate increased significantly,while this was not the case in patients with normal renal function before TIPS placement.Hepatic function did not change significantly after TIPS placement and no significant decline in ADMA plasma levels was measured.CONCLUSION:The increase of the arginine/ADMA ratio after TIPS placement suggests an increase in intracellular NO bioavailability.In addition,this study suggests that TIPS placement does not alter dimethylarginine dimethylaminohydrolase(DDAH) activity and confirms the major role of the liver as an ADMA clearing organ.

Determination of Asymmetric Dimethylarginine and Symmetric Dimethylarginine in Biological Samples of Mice Using LC/MS/MS

Herein, we present a novel method of asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) determination within biological samples using protein precipitation and LC/MS/MS. Chromatographic separation of ADMA and SDMA was successfully performed using a silica column with optimized elution, or mobile phase, of 10 mM ammonium acetate buffer H2O/methanol/acetonitrile (20/30/45, v/v) at pH 4. The calibration ranges were 0.50 – 50.0 μg●mL-1, and good linearities were obtained for all compounds ( γ > 0.99). The intra- and inter-assay accuracies with recoveries and precisions at three concentration levels (i.e. 1.00, 5.00 and 25.0 μg●mL-1) were better than 86.9% and 7.36%, respectively. The analytical performance of the method was evaluated by determination of compounds in plasma, urine and tissues from male BALBc/J mice. For the first time, we were able to characterize the distribution of ADMA, SDMA and ADMA/SDMA in plasma, urine, brain, heart, kidneys, liver, lungs, pancreas and spleen. Additionally, we demonstrated that the ADMA/SDMA ratio in the brain was approximately 10-fold lower than all the other biological samples. Only 10 μL of plasma, 1 μL of urine and about 25 mg of tissues were required. These results suggest that the developed methodology was useful in ADMA and SDMA determination within biological samples.

Plasma Asymmetric Dimethylarginine Levels in Neonates with Bronchopulmonary Dysplasia Associated with Pulmonary Hypertension

Background: Bronchopulmonary dysplasia (BPD) continues to be an important problem in neonates especially premature infants despite improved facilities of care, monitoring and treatment. Pulmonary hypertension (PH) is a major complicating factor and key cause of mortality in this population. Altered vascular and alveolar growth particularly in canalicular and early saccular stages of lung development following mechanical ventilation and oxygen therapy result in arrest of the lung development leading to BPD with PH. Early recognition of PH in infants with these risk factors is important for optimal management. We tested the hypothesis that asymmetric dimethylarginine, would be greater in infants with bronchopulmonary dysplasia associated pulmonary hypertension than in infants with BPD alone. The Aim: The aim of the current study was to measure the Asymmetric dimethylarginine (ADMA) levels, arginine levels & the plasma arginine-to-ADMA ratio in newborn infants with broncho-pulmonary dysplasia, to evaluate echocardiographic parameters among neonates with bronchopulmonary dysplasia, to correlate between plasma ADMA & arginine-to-ADMA ratio and echocardiographic (ECHO) parameters in those patients and to compare full term & preterm neonates with bronchopulmonary dysplasia as regard to plasma ADMA level. Methods: A case-control study was carried out of ninety (90) newborns selected from those admitted to Neonatal Intensive Care Unit at Maternity & Children Hospital and Alzhraa University hospital during the period from October 2015 to March 2018. Neonates were divided into 2 groups: Patient with BPD with PH (cases group): It included 45 neonates with BPD & PH, 35 preterm neonates and 10 full term neonates. Patient with BPD only (Control group): It included 45 neonates with BPD without PH. These 45 neonates were divided as 22 preterm neonates and 23 full term neonates. Laboratory work was done in Alzhraa University hospital. Asymmetric dimethylarginine (ADMA) levels & arginine levels were measured using competitive enzyme linked immune-assay (ELISA). Results: Patients with both BPD and PH had greater plasma levels of ADMA than patients with BPD alone (P value 0.000). ADMA level > 186 ng/dl can predict development of PH in patient with BPD with sensitivity 100% and specify 100%. Preterm neonates with BPD had greater level of ADMA than full term neonates (P value 0.002). There was no statically significance difference between level of ADMA if withdrawn before or after 28 days of age (range of age at time of sampling in our study was 23 - 40 days) (P value 0.878), even ADMA level increased above the cut point early in the disease before we screened some cases by ECHO. There was no statically significance difference between level of arginine in cases and control groups with P value 0.530. The plasma arginine-to-ADMA ratio was lower in cases than in controls suggesting a greater likelihood of inhibition of nitric oxide production in patients with both BPD and PH than in patients with BPD alone (P value 0.000). ADMA level can predict severity of pulmonary hypertension in patient with BPD, as it was positively correlated with the grade of pulmonary hypertension (P value 0.006). ADMA level is higher in neonates with BPD and PH who died than those who survived;it can predict death in neonates with BPD &PH at cut off point > 643 ng/dl. Conclusion: ADMA increased in newborn infants with BPD, who developed PH. ADMA may have diagnostic and prognostic values. ADMA level was higher in preterm neonates than full term neonates and its level was correlated positively with severity of PH. ADMA levels were significant higher in infants with BPD with PH who died later than those who survived. There was no statically significance difference between levels of ADMA, whether it was drawn before or after 28 days of age (range 23 - 40 days). Echocardiographic screening and ADMA measurement could help in prevention of PH, diagnosis and early treatment of newborn infants suffering from BPD.

血清ADMA、IL-6、内毒素及乳酸在新生儿败血症所致感染性休克中的表达及临床意义

目的探讨血清不对称二甲基精氨酸(ADMA)、白细胞介素-6(IL-6)、内毒素及乳酸在新生儿败血症所致感染性休克中的表达及临床意义。方法选取我院收治的58例新生儿败血症所致感染性休克患儿为休克组,62例新生儿败血症未发生感染性休克患儿为败血症组,60例无感染新生儿为对照组。检测所有研究对象血清中的ADMA、IL-6、内毒素及乳酸水平。比较三组研究对象的ADMA、IL-6、内毒素及乳酸水平;分析ADMA、IL-6、内毒素及乳酸水平对新生儿败血症所致感染性休克患儿的诊断价值;分析ADMA水平与IL-6、内毒素及乳酸水平的关系;分析ADMA、IL-6、内毒素及乳酸水平与休克组预后的关系。结果休克组的ADMA、IL-6、内毒素及乳酸水平均高于败血症组及对照组(P<0.05);败血症组的ADMA、IL-6、内毒素水平均高于对照组(P<0.05);败血症组和对照组的乳酸水平无显著差异(P>0.05)。受试者工作特征曲线(ROC)结果显示,ADMA、IL-6、内毒素及乳酸诊断新生儿败血症所致感染性休克的曲线下面积(AUC)分别为0.93、0.89、0.89、0.92。Pearson相关性分析结果显示,ADMA水平与IL-6、内毒素及乳酸水平呈正相关(P<0.05)。ADMA、IL-6、内毒素及乳酸高水平与新生儿败血症所致感染性休克预后不良有关。结论血清ADMA、IL-6、内毒素及乳酸在新生儿败血症所致感染性休克中表达水平较高,可作为该疾病诊断的生物标志物并预测预后。

孕早期及孕中期血清PP-13和ADMA对子痫前期孕妇分娩方式的预测价值

目的分析孕早期、孕中期血清半乳糖凝集素-13(PP-13)、非对称性二甲基精氨酸(ADMA)对子痫前期孕妇分娩方式的预测价值。方法回顾性收集2020年1月至2022年12月在该院产科分娩的120例孕妇的临床资料,其中子痫前期孕妇76例,按照子痫前期严重程度分为轻度组52例、重度组24例,另选取同期正常孕妇44例作为对照组,采用酶联免疫吸附试验(ELISA)检测PP-13和ADMA水平。比较3组研究对象PP-13、ADMA水平,比较不同分娩方式孕妇PP-13、ADMA水平,绘制受试者工作特征(ROC)曲线分析PP-13、ADMA预测子痫前期孕妇分娩方式的效能。结果孕早期及孕中期PP-13水平均为重度组<轻度组<对照组,且任意两组间比较,差异均有统计学意义(P<0.05);而孕早期及孕中期ADMA水平均为重度组>轻度组>对照组,且任意两组间比较,差异有统计学意义(P<0.05)。剖宫产比例为重度组>轻度组>对照组,自然分娩比例及阴道助产比例为重度组<轻度组<对照组,且任意两组间比较,差异均有统计学意义(P<0.05)。自然分娩孕妇孕早期、孕中期PP-13水平均高于其他分娩方式孕妇,ADMA水平均低于其他分娩方式孕妇,差异均有统计学意义(P<0.05)。ROC曲线分析显示,孕早期PP-13、孕早期ADMA、孕中期PP-13、孕中期ADMA预测子痫前期孕妇自然分娩的曲线下面积(AUC)分别为0.806、0.963、0.781、0.673。结论孕早期PP-13、孕早期ADMA、孕中期PP-13可能可以用于子痫前期孕妇分娩方式的预测。

C1q、Lp-PLA2、ADMA对原发性高血压患者心血管事件发生风险的评估价值

目的 分析补体1q(C1q)、脂蛋白相关磷脂酶A2(Lp-PLA2)、非对称二甲基精氨酸(ADMA)对原发性高血压患者心血管事件发生风险的评估价值。方法 2021年1月至2023年2月新郑华信民生医院收治的156例原发性高血压并发心血管事件患者纳入研究组,另择同期168例原发性高血压未并发心血管事件患者纳入对照组。分析两组临床特征、常规生化指标、血清C1q、Lp-PLA2、ADMA水平,通过多因素分析法分析原发性高血压患者发生心血管事件的危险因素,绘制受试者工作特征(ROC)曲线分析相关指标对原发性高血压患者发生心血管事件的评估价值。结果 多因素logistic分析结果显示,体重指数(BMI)升高、合并糖尿病、高血压分级3级、血清Lp-PLA2及ADMA水平升高为原发性高血压患者发生心血管事件的危险因素(OR=1.988、2.063、2.020、2.083、2.326,P<0.05);血清C1q水平升高为原发性高血压患者发生心血管事件的保护因素(OR=0.534,P<0.05)。将原发性高血压患者发生心血管事件纳入阳性,未发生心血管事件纳入阴性,绘制ROC曲线分析C1q、Lp-PLA2、ADMA单独及联合检测对原发性高血压患者发生心血管事件的评估价值,曲线下面积(AUC)为0.785、0.852、0.781、0.916,敏感度为75.00%、79.49%、69.23%、89.74%,特异度为67.86%、79.76%、78.57%、81.55%,联合检测均最高。结论 原发性高血压患者心血管事件发生的危险因素包括BMI升高、合并糖尿病、高血压分级3级、血清C1q水平降低、Lp-PLA2、ADMA水平升高,C1q、Lp-PLA2及ADMA联合检测对原发性高血压患者心血管事件发生风险的评估价值较高,可为临床干预方案的选择提供依据。

葛根素对氧自由基培养的脐静脉内皮细胞ADMA-DDAH系统的影响

目的观察葛根素对氧自由基(oxidized free radical,OFR)培养的人脐静脉内皮细胞(human um-bilical vein endothelial cells,HUVECs)二甲基精氨酸-二甲基赖氨酸水解酶(di methylarginine di methy-laminohydrolase,DDAH)活性及表达的影响,以探讨葛根素对不对称二甲精氨酸(ADMA)代谢机制的影响。方法采用改良的Jaffe法培养原代HUVECs,取生长良好的3～6代HUVECs用于实验,分为(1)空白对照组:加DMEM培养液;(2)OFR组:加入OFR0.1mmol/L;(3)葛根素Ⅰ组:加0.1mmol/L OFR及0.5mg/ml葛根素;(4)葛根素Ⅱ组:加0.1mmol/L OFR和1.0mg/ml葛根素。共孵24h后,检测上清液中NO、NOS活性、ET、ADMA含量、L-胍氨酸(L-cit)浓度,采用Western blotting测定细胞裂解液中DDAH的蛋白表达。结果OFR条件培养下,内皮细胞的代谢产物ADMA、ET含量均较空白对照组高,而NO及NOS的活性减少;反应DDAH酶活性的L-cit浓度显著降低,而DDAH的表达无明显变化。葛根素干预后,ADMA、ET含量较OFR组降低,NOS活性及NO增加,L-cit浓度明显升高。结论OFR培养下,内皮损伤ADMA的增加与DDAH的活性减弱有关,而与DDAH的表达无关。葛根素通过增加DDAH活性促进ADMA代谢,使NOS活性增加,抑制OFR对内皮功能的损伤。

卡托普利对动脉粥样硬化家兔血管内皮功能的保护作用及其机制

目的探讨卡托普利对动脉粥样硬化(AS)家兔血管内皮功能和形态的保护作用及其机制。方法采用高脂、高胆固醇饲料饲养家兔制备AS模型的同时口服给予卡托普利8 mg·kg-1,每天1次,连续12周;HE染色观察血管组织形态,检测血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL)和高密度脂蛋白(HDL);高效液相色谱测定血清非对称性二甲基精氨酸(ADMA)浓度;用重组编码人类二甲基精氨酸-二甲胺水解酶2(hDDAH2)基因的腺病毒感染AS家兔离体胸主动脉环2 h,检测对乙酰胆碱累积浓度诱导的最大舒张反应(Emax)、半数有效量(EC50)及DDAH活性。结果与正常组比较,高脂模型家兔胸主动脉内膜和中膜增厚,血清TC,TG和LDL水平升高;血清ADMA浓度升高至(2.24±0.28)μmol·L-1(P<0.01);血管壁DDAH活性降至(0.048±0.007)U·g-1蛋白(P<0.01);Emax降低至(56±8)%(P<0.01),EC50升高至(158±52)nmol·L-1(P<0.01)。与AS模型组比较,卡托普利治疗组血管内膜增厚减轻,血脂无明显降低,血清ADMA浓度显著降低至(1.37±0.23)μmol·L-1(P<0.01),血管DDAH活性增加至(0.084±0.013)U·g-1蛋白(P<0.01),内皮依赖性血管舒张功能改善,Emax增加至(88±4)%(P<0.01),EC50降低至(90±35)nmol·L-1(P<0.01)。AS模型血管转染DDAH2基因后,血管Emax回升至(88±4)%,EC50降低至(98±42)nmol·L-1,DDAH活性升高至(0.112±0.017)U·g-1蛋白,与卡托普利治疗组相似。结论卡托普利对AS家兔血管形态和内皮功能具有明显保护作用,其机制可能与增加血管DDAH活性,降低内源性ADMA浓度有关。

血压盐敏感者一氧化氮系统与非对称性二甲基精氨酸和补钾的作用

目的通过观察慢性盐负荷及补钾后血浆非对称性二甲基精氨酸(ADMA)和血、尿一氧化氮(NO)水平的变化及其与血压的关系,探讨血压正常盐敏感者(SS)的血管内皮功能损伤及补钾的保护作用。方法选60例年龄在20～60岁的血压正常者参与为期3周的慢性盐负荷及补钾试验,包括基线调查3d,低盐(LS)饮食,高盐(HS)饮食,和高盐补钾(HS+K)饮食各7d的研究。每个阶段均测量血压,并收集血、尿标本。血、尿NO用Griess法测量,血浆ADMA用高效液相色谱法测量。结果受试者60例中共检出SS13例,检出率为21.6%。盐负荷后,SS血浆ADMA的浓度明显升高[(0.89±0.09vs0.51±0.07)μmol/L,P<0.05],而血浆NO的水平则较LS饮食期显著降低[(41.8±7.6vs63.5±7.6)μmol/L,P<0.01]。在HS摄入的基础上大剂量口服补钾可以逆转单纯HS负荷对SS血浆ADMA浓度和血、尿NO水平的作用[(ADMA:0.52±0.09vs0.89±0.09)μmol/L;NO:(58.1±7.4vs41.8±7.6)μmol/L],血浆ADMA浓度和平均动脉压之间存在正相关关系。结论血压正常SS于HS负荷后伴随血压升高,血浆ADMA显著升高、NO降低,同时补充钾盐可以逆转前述作用,提示补钾可能通过抑制ADMA的升高降低血压。

同型半胱氨酸对内皮细胞一氧化氮合酶系统的损伤机制及叶酸的拮抗效应

本实验探讨同型半胱氨酸(Hcy)对人脐静脉内皮细胞(HUVEC)一氧化氮合酶(eNOS)的损伤机制及叶酸(FA)的拮抗效应。HUVEC原代培养,传至第3代后,将其与不同浓度Hcv(10μmol/L、30μmol/L、100μmol/L和300μmol/L)、FA(100μmol/L)或两者联合共同培养72h,用RT-PCR和免疫组织化学技术分别估测细胞eNOS mRNA水平及eNOS蛋白质量;高效液相色谱测定细胞内不对称二甲基精氨酸(ADMA)含量;并分别测定二甲基精氨酸二甲胺水解酶(DDAH)、eNOS活性及一氧化氮(NO)含量。HUVEC与不同浓度Hcy培养72h后,eNOS mRNA和蛋白质表达皆受到抑制;eNOS活性降低;NO生成减少。同时,DDAH活性降低;细胞内ADMA含量呈剂量依赖性增加。加入FA后,eNOS蛋白质水平上调;eNOS活性增强;NO生成增多。同时,DDAH活性增强,ADMA蓄积减少;但eNOS mRNA表达没有改变。Hcy对内皮细胞eNOS的损伤机制涉及eNOS酶蛋白和eNOS的基因表达两个层面,其对eNOS酶蛋白的抑制机制可能通过DDAH-ADMA通路,FA可拮抗Hcy对eNOS酶蛋白的抑制作用,显示出对HHcy有一定的保护作用。但FA对HHcy所导致的eNOS基因表达的抑制无保护效应。

血清不对称性二甲基精氨酸浓度变化与慢性肾衰高血压相关性探讨

采用高效液相色谱方法 (HPLC)检测 2 9例血液透析患者血、尿不对称性二甲基精氨酸 (asymmetricdimeth ylarginine ,ADMA)的浓度 ,并与血压作相关性分析。结果表明 :血液透析患者血清ADMA浓度明显升高 ,尿ADMA浓度降低 ,与正常对照组比较差异有显著性 (P <0 .0 1) ;血清ADMA浓度与收缩压及舒张压呈明显正相关 (分别为 r=0 .6 34,P <0 .0 1;r =0 .735 ,P <0 .0 1)。结果提示血液透析患者体内ADMA浓度增高 。

瑞格列奈和格列齐特缓释片对新诊断2型糖尿病患者血清非对称性二甲基精氨酸的影响

目的比较瑞格列奈和格列齐特缓释片对新诊断2型糖尿病餐后血糖、血清真胰岛素、非对称性二甲基精氨酸水平的影响。方法新诊断2型糖尿病患者40例随机分为瑞格列奈组和格列齐特缓释片组,进行为期4周的随机平行对照研究,两种药物治疗前后测定空腹和标准餐后血糖、血清真胰岛素和非对称性二甲基精氨酸水平,并用早期胰岛素分泌指数评价早相胰岛素分泌功能。结果瑞格列奈和格列齐特缓释片降低餐后血糖的效果相似;瑞格列奈较格列齐特缓释片显著改善早期胰岛素分泌指数(P=0.018);瑞格列奈能显著降低餐后240 min血清非对称性二甲基精氨酸水平(P=0.012);格列齐特缓释片能显著降低餐后180 min(P=0.014)和240 min血清非对称性二甲基精氨酸水平(P=0.002)。结论瑞格列奈和格列齐特缓释片对新诊断的2型糖尿病患者的总降糖效果相当;瑞格列奈可改善早相胰岛素分泌,其作用强于格列齐特缓释片;瑞格列奈和格列齐特缓释片均能降低餐后血清非对称性二甲基精氨酸水平,提示这两种促泌剂在改善2型糖尿病患者血管内皮功能障碍,延缓其大血管并发症发生和发展方面有一定作用。

氯沙坦保护ox-LDL诱导的内皮细胞损伤与ADMA的关系

目的：探讨氯沙坦对氧化型低密度脂蛋白（ox-LDL）诱导的内皮细胞损伤的保护作用及其与内源性一氧化氮合酶抑制物非对称性二甲基精氨酸（ADMA）的关系。方法：用ox-LDL（100mg／L）孵育人脐静脉内皮细胞株HUVEC12 24h或用10^-8～10^-6mmol／L的氯沙坦预孵育HUVEC12 30min后再与ox-LDL共孵育24h，测定培养液中乳酸脱氢酶（LDH）活性、一氧化氮（NO）、肿瘤坏死因子-α（TNF-α）、ADMA含量和细胞内二甲基精氨酸二甲胺水解酶（DDAH）活性。结果ox-LDL孵育HUVEC12细胞24h后细胞培养液中LDH活性、TNF-α和ADMA含量明显增加（P〈0．05），同时NO含量下降和细胞DDAH酶活性受到抑制（P〈0．05）；氯沙坦（10^-8～10^-6mmoL／L）可显著减轻ox-LDL诱导的LDH活性、TNF-α和ADMA含量的增加以及NO含量的降低（P〈0．05），并呈浓度依赖性的增加DDAH活性（P〈0.05）。结论：氯沙坦对ox-LDL诱导的血管内皮细胞损伤具有保护作用，该作用可能与增加DDAH活性，降低ADMA浓度有关。

同型半胱氨酸对内皮细胞一氧化氮合酶活力及基因表达的影响

目的观察同型半胱氨酸(Hcy)对培养的人脐静脉内皮细胞(HUVEC)一氧化氮合酶(eNOS)活力及其基因表达的动态影响。方法10、30、100、300μmol.L-1Hcy与HUVEC分别培养24、48、72 h后,用HPLC测定细胞内不对称二甲基精氨酸(ADMA)的含量,反转录聚合酶链反应(RT-PCR)检测细胞内eNOS mRNA的表达,并分别测定细胞二甲基精氨酸二甲基氨基水解酶(DDAH)、eNOS的活力和NO的含量。结果HUVEC经不同浓度Hcy分别处理24、48、72 h后,其细胞内ADMA聚积增多,DDAH活性和eNOS活力降低,NO生成减少,且呈时间和浓度依赖性。但只有100μmo.lL-1Hcy与HUVEC作用72 h时,才引起eNOS mRNA表达的减少。结论Hcy对内皮功能的损伤可能通过抑制DDAH活性,引起ADMA聚积,从而降低eNOS活力,导致NO生成减少。此外,eNOS mRNA表达的抑制也是Hcy诱导的内皮功能障碍的机制之一。

奥卡西平和丙戊酸钠对成人部分性癫痫患者脑电图及相关血液学指标水平的影响

目的研究奥卡西平和丙戊酸钠对成人部分性癫痫患者脑电图及外周血同型半胱氨酸(Hcy)和不对称二甲基精氨酸(ADMA)水平的影响。方法于2014年5月至2015年5月,将100例成人部分性癫痫患者随机分为治疗组(奥卡西平治疗)和对照组(丙戊酸钠治疗),每组各50例。观察治疗后患者脑电图指标、Hcy、ADMA、认知功能变化及不良反应发生情况。结果治疗前,两组患者脑电图指标检查结果比较差异无统计学意义(P>0.05);治疗后,两组患者α波减少超过0.5 Hz、θ波增多、δ波增多发生率比较差异有统计学意义(P<0.05)。治疗前,两组患者血清Hcy、ADMA水平比较差异无统计学意义(P>0.05);治疗后,两组患者血清Hcy、ADMA水平均显著升高(P<0.05)。治疗前,两组患者简明精神状态检查量表(MMSE)评分比较差异无统计学意义(P>0.05);治疗后,治疗组患者MMSE评分高于对照组(P<0.05)。治疗组患者中,出现皮疹1例、胃肠道不适2例,均自行好转;对照组患者中,出现眩晕3例、皮疹5例、胃肠道不适1例,均自行好转。结论奥卡西平与丙戊酸钠对外周血Hcy、ADMA水平的影响类似;与丙戊酸钠相比,奥卡西平可显著改善癫痫患者认知功能。

原发性高血压患者血浆非对称性二甲基精氨酸浓度升高

背景非对称性二甲基精氨酸是一种内源性一氧化氮(NO)合成酶抑制剂,可以抑制NO的生成,影响血管内皮功能。目的探讨原发性高血压患者血浆非对称性二甲基精氨酸(ADMA)浓度的变化及可能意义。方法选取经冠状动脉造影检查排除冠状动脉粥样硬化性心脏病且无糖尿病的住院病人56例,其中原发性高血压(EH)患者30例,对照组(26例)为血压正常并无高血压史患者。通过高效液相色谱联合质谱法(HPLC)测定各患者的血浆ADMA、L精氨酸(L-Arg)含量,比色法测定血糖、肌酐、尿素氮、高密度脂蛋白胆固醇(HDL-C)、总胆固醇(TC)、三酰甘油(TG)和尿酸(UA)。结果EH组血浆ADMA浓度[(0.029±0.010)mmol/L]显著高于对照组[(0.023±0.010)mmol/L,P<0.05]。两组间血浆L-Arg、HDL-C、TC、TG、UA浓度比较,差异无统计学意义(P>0.05)。血浆ADMA、L-Arg浓度与患者年龄、HDL-C、TC、TG、UA浓度无相关性(P>0.05)。结论EH患者血浆ADMA浓度升高。