血清尿酸对心血管系统及神经退行性病变的影响

尿酸是人体嘌呤代谢的最终产物。高尿酸血症,即血清尿酸水平过高,是引发痛风的主要病因。越来越多的流行病学研究将高尿酸血症与心血管系统疾病和神经退行性病变紧密联系在一起。这些研究表明,炎性反应极有可能是高尿酸水平引发痛风的致病机制。同时,炎性反应与尿酸引起的心血管系统改变息息相关。尿酸钠晶体被认为通过Toll样受体家族诱发炎症反应诱导炎症的发生。此外,可溶性尿酸可以促进自由基的生成,起到促进氧化的作用。本综述总结了近期关于高尿酸血症和心血管系统疾病的流行病学研究,简要回顾了高尿酸血症在神经退行性病变中的作用,并描述了尿酸诱导的炎症产生机制。     

基于肠道菌群防治高尿酸血症的研究进展

高尿酸血症是由嘌呤代谢异常引起尿酸生成过多和(或)排泄减少导致血尿酸超出正常范围的代谢性疾病.目前研究已证实,促进尿酸合成的酶在肠道中高表达,人体1/3的尿酸经肠道排泄.随着微生物学研究的快速发展,肠道菌群的研究也逐渐深入,发现高尿酸血症患者肠道菌群的结构和数量均发生变化,肠道菌群可能是高尿酸血症的肠道触发因素.肠道菌...     

肠道菌群与高尿酸血症及痛风的相关性研究

高尿酸血症以及痛风的发病率持续升高,已经成为一个重大的公共卫生问题。肠道菌群的结构改变或失调可引起机体代谢紊乱,肠道微生态尤其与代谢性疾病的发生发展关系密切。目前研究发现高尿酸血症、痛风患者存在肠道菌群失调,降尿酸治疗后肠道菌群可发生相应改变,并且益生菌制剂具有降尿酸作用。本文概述高尿酸血症及痛风患者的肠道菌群特点,从高嘌呤及高果糖饮食对肠道菌群的影响、肠道参与嘌呤和尿酸的代谢、代谢性内毒素血症以及痛风相关炎症因子等方面探讨肠道菌群与高尿酸血症及痛风的关系,并展望肠道菌群可能成为未来诊治高尿酸血症以及痛风的一种新方法。     

体外合成的ABC转运蛋白2 mRNA在小鼠体内表达促进尿酸排泄

高尿酸血症是指嘌呤代谢紊乱尿酸在体内堆积所导致的慢性代谢疾病,近年来其发病率增高且发病年龄呈现年轻化趋势,寻找有效的治疗靶点以及治疗方法是当前研究的热点.尿酸盐转运蛋白 ABC 转运蛋白2(ATP-binding cassette subfamily G member 2,ABCG2)主要表达于肾,促进尿酸排泄.本研究...     

血清尿酸水平与冠心病的相关性研究

目的:众多关于血清尿酸水平与冠心病发展预后的相关性研究结果不一。本研究旨在通过对上海市第一人民医院入院患者的临床资料分析,研究血清尿酸水平与冠心病之间关系。方法:选择2008年7月至2009年4月上海地区、汉族就诊于我院的患者(123例),按入选排除标准,将入院患者分为冠心病组和对照组,分析尿酸水平与冠心病的关系。结果:男性(81.4%vs 51.6%)、吸烟(49.2%vs 21.9%)、血清尿酸水平升高(6.10±1.2 mg/dl vs 5.37±1.5 mg/dl)为冠心病的危险因素,统计值分别为0.02,0.02,0.005。血尿酸水平升高与血管病变严重程度成正相关,除单支血管病变外,双支血管病变患者尿酸水平为(6.11±1.07)mg/dl,对照组为(5.37±1.55)mg/dl,P0.05,三支病变患者尿酸水平为(6.84±1.29)mg/dl,P0.05。结论:血清尿酸水平升高与冠心病的发生、及病变严重程度密切相关。对冠心病患者的预防和治疗中,应重视对尿酸水平的监测。尿酸水平能否作为冠心病患者预后、转归的预测因子以及降低尿酸水平的治疗能否给冠心病患者带来收益有待进一步的研究。     

痛风性关节炎动物模型的研究现状与展望

痛风是由于机体嘌呤代谢紊乱,导致血内尿酸增高和/或肾脏排泄尿酸减少,从而引起尿酸盐在组织沉积的疾病,目前尚未见在实验动物中复制出类似人类的痛风性关节炎模型。通过对目前国内外高尿酸血症及痛风模型复制的方法、机制和应用的研究,分析各自的特点及不足之处,并提出复制更加符合临床的高尿酸血症及痛风性关节炎动物模型的展望与设想。     

高尿酸血症和痛风的流行病学及其危险因素的研究进展

高尿酸血症和痛风是由于长期嘌呤代谢紊乱所引起的一种代谢性疾病,随着各国经济的发展,其患病率在全球范围呈逐年升高的趋势,因此相关研究也日益增多.本文就近年来有关高尿酸血症与痛风的流行病学及其危险因素的研究作一综述,并着重阐述高尿酸血症与糖尿病关系的相关研究进展.     

绞股蓝皂苷对高尿酸血症大鼠血尿酸的影响

高尿酸血症是近年来日益多发的代谢综合征。本研究探讨绞股蓝皂苷提取物对高尿酸血症大鼠血清尿酸的影响及作用方式。研究采用高尿酸血症大鼠动物模型,生化检测,代谢实验方法等,对摄入绞股蓝皂苷提取物的实验大鼠的血清尿酸水平,尿酸生成关键酶黄嘌呤氧化酶活性,24 h尿液酸碱度、尿酸浓度及尿酸排泄量等指标进行监测。结果发现,绞股蓝皂苷可以通过抑制尿酸生成,促进排泄,抑制机体的血尿酸水平升高,有益于改善高尿酸血症患者健康状况。     

尿酸与心血管疾病的关系

尿酸(uric acid, UA)是人体内嘌呤代谢的终产物。在心血管系统中,尿酸可激活肾素-血管紧张素系统、引起内皮细胞功能障碍及炎症反应,与心血管疾病的发生发展相关。本文就尿酸的生理功能、与心血管疾病(高血压、心房颤动、动脉粥样硬化、冠心病、急性心肌梗死)之间的关系及临床药物研究进展进行综述,概述目前高尿酸血症与心血管疾病相关研究进展,阐述二者之间的相关性,有利于早期诊疗心血管疾病,预防心血管疾病不良事件发生给患者带来的危害。     

肾脏尿酸转运体的研究进展

尿酸是人体内嘌呤代谢的终产物。在肝脏合成后,正常情况下约70%的尿酸在肾脏分泌,而一小部分则被分泌到肠内。肾脏是血尿酸稳态调节的主要器官,其调控依赖于尿酸转运体的转运。尿酸代谢紊乱或转运异常将导致高尿酸血症、痛风、痛风性肾结石等疾病。本文对肾脏尿酸转运体的研究进展进行综述。     

患儿体外循环直视心脏术后高尿酸血症分析

目的：探讨体外循环心脏术后24h患儿高尿酸血症发生的原因、影响因素和预后。方法：以2006年9～12月我院心脏外科收治的106例体外循环心脏手术患儿为研究对象,收集其年龄、体外循环时间、尿量、预后资料和心脏术后24h血尿酸、尿素氮、肌酐、胱抑素、血糖、总胆红素、直接胆红素等生化指标数据;以空腹血尿酸为标准,将患儿分为无高尿酸血症组和高尿酸血症组,用SPSS11．0软件分析两组之间临床资料的差异、高尿酸血症组血尿酸与其他指标的相关性及影响患者预后的因素。结果：患儿术后高尿酸血症组患者53例（50％）,与无高尿酸血症组相比P〈0．01,除年龄因素外,其他临床指标均有统计学意义;高尿酸血症组的血尿酸与血糖、总胆红素无相关性,与年龄、尿量呈显著负相关,与转流时间、尿素氮、肌酐、胱抑素、直接胆红素含量呈极显著正相关;在预后良好组与死亡组的比较中,转流时间、血尿酸、尿素氮、肌酐含量有统计学意义。结论：患儿体外循环心脏术后高尿酸血症的发生较常见,血尿酸水平对患者术后肾功能状态及预后具有重要临床意义,连续监测术后血尿酸、尿素氮、肌酐水平是及时判断患者临床状况以采取相应措施改善预后的重要方法;低心排血量综合征是引起患者死亡的危险因素之一,通过提高体外循环心脏手术水平,尽量缩短转流时间,加强围手术期监护,可有效减少术后并发症,降低死亡率。     

齿孔酸对高尿酸血症黄嘌呤氧化酶活性的影响

采用紫外分光光度法检测齿孔酸在体外对黄嘌呤氧化酶的作用,并进行动力学研究探讨其作用机制;采用酵母联合氧嗪酸钾诱导高尿酸血症小鼠模型,观察齿孔酸对高尿酸血症小鼠血清尿酸水平、血清黄嘌呤氧化酶活性、肝脏黄嘌呤氧化酶活性及血糖血脂的影响。研究发现,齿孔酸体在外能抑制黄嘌呤氧化酶活性,降低高尿酸血症小鼠血清尿酸水平、血清黄嘌呤氧化酶活性、肝脏黄嘌呤氧化酶活性,同时明显降低空腹血糖、总胆固醇、甘油三酯、低密度脂蛋白胆固醇水平,升高高密度脂蛋白胆固醇水平,提高口服糖耐受量。结果表明,齿孔酸是黄嘌呤氧化酶竞争性抑制剂,还能缓解高尿酸血症小鼠糖脂代谢紊乱,对高尿酸血症及痛风的防治具有潜在意义。     

齿孔酸对高尿酸血症黄嘌呤氧化酶活性的影响

采用紫外分光光度法检测齿孔酸在体外对黄嘌呤氧化酶的作用,并进行动力学研究探讨其作用机制;采用酵母联合氧嗪酸钾诱导高尿酸血症小鼠模型,观察齿孔酸对高尿酸血症小鼠血清尿酸水平、血清黄嘌呤氧化酶活性、肝脏黄嘌呤氧化酶活性及血糖血脂的影响。研究发现,齿孔酸体在外能抑制黄嘌呤氧化酶活性,降低高尿酸血症小鼠血清尿酸水平、血清黄嘌呤氧化酶活性、肝脏黄嘌呤氧化酶活性,同时明显降低空腹血糖、总胆固醇、甘油三酯、低密度脂蛋白胆固醇水平,升高高密度脂蛋白胆固醇水平,提高口服糖耐受量。结果表明,齿孔酸是黄嘌呤氧化酶竞争性抑制剂,还能缓解高尿酸血症小鼠糖脂代谢紊乱,对高尿酸血症及痛风的防治具有潜在意义。     

Hyperuricemia in Hematologic Malignancies Is Caused by an Insufficient Urinary Excretion

In order to elucidate the mechanism of hyperuricemia in hematologic malignancies, we have retrospectively investigated the uric acid metabolism in 418 chemotherapy-naïve patients with hematologic malignancies. Hyperuricemia was present in 116 (27.8%) of these patients on initial hospitalization. Among 65 hyperuricemic patients analyzed uric acid metabolism, six (9.2%) had overproduction type, 52 (80.0%) had underexcretion type, and seven (10.8%) had a mixed type. Fourteen patients (3.3%) developed tumor lysis syndrome in 418 patients.     

Hyperuricemia enhances intracellular urate accumulation via down-regulation of cell-surface BCRP/ABCG2 expression in vascular endothelial cells

Hyperuricemia has been recognized as an independent risk factor for cardiovascular disease. Urate stimulates NADPH oxidase and induces production of reactive oxygen species (ROS); consequently, intracellular urate accumulation can induce oxidative stress leading to endothelial dysfunction. Here, we studied the mechanism involved, using human umbilical vascular endothelial cells (HUVEC) as a model. Pretreatment with 15 mg/dL unlabeled uric acid (corresponding to hyperuricemia) resulted in increased uptake of [¹⁴C]uric acid at steady-state by HUVEC, whereas pretreatment with 5 mg/dL uric acid (in the normal serum concentration range) did not. However, the initial uptake rate of [¹⁴C]uric acid was not affected by uric acid at either concentration. These results suggest that efflux transport of uric acid is decreased under hyperuricemic conditions. We observed a concomitant decrease of phosphorylated endothelial nitric oxide synthase. Plasma membrane expression of breast cancer resistance protein (BCRP), a uric acid efflux transporter, was decreased under hyperuricemia, though the total cellular expression of BCRP remained constant. Uric acid did not affect expression of another uric acid efflux transporter, multidrug resistance associated protein 4 (MRP4). Moreover, phosphorylation of Akt, which regulates plasma membrane localization of BCRP, was decreased. These uric acid-induced changes of BCRP and Akt were reversed in the presence of the antioxidant N-acetylcysteine. These results suggest that in hyperuricemia, uric acid-induced ROS generation inhibits Akt phosphorylation, causing a decrease in plasma membrane localization of BCRP, and the resulting decrease of BCRP-mediated efflux leads to increased uric acid accumulation and dysregulation of endothelial function.     

Hyperuricemia and Risk of Incident Hypertension: A Systematic Review and Meta-Analysis of Observational Studies

Background

Observational studies of the relationship between hyperuricemia and the incidence of hypertension are controversial. We conducted a systematic review and meta-analysis to assess the association and consistency between uric acid levels and the risk of hypertension development.

Methods

We searched MEDLINE, EMBASE, CBM (Chinese Biomedicine Database) through September 2013 and reference lists of retrieved studies to identify cohort studies and nested case-control studies with uric acid levels as exposure and incident hypertension as outcome variables. Two reviewers independently extracted data and assessed study quality using Newcastle-Ottawa Scale. Extracted information included study design, population, definition of hyperuricemia and hypertension, number of incident hypertension, effect sizes, and adjusted confounders. Pooled relative risks (RRs) and corresponding 95% confidence intervals (CIs) for the association between hyperuricemia and risk of hypertension were calculated using a random-effects model.

Results

We included 25 studies with 97,824 participants assessing the association between uric acid and incident hypertension in our meta-analysis. The quality of included studies is moderate to high. Random-effects meta-analysis showed that hyperuricemia was associated with a higher risk of incident hypertension, regardless of whether the effect size was adjusted or not, whether the data were categorical or continuous as 1 SD/1 mg/dl increase in uric acid level (unadjusted: RR = 1.73, 95% CI 1.46∼2.06 for categorical data, RR = 1.22, 95% CI 1.03∼1.45 for a 1 SD increase; adjusted: RR = 1.48, 95% CI 1.33∼1.65 for categorical data, RR = 1.15, 95% CI 1.06∼1.26 for a 1 mg/dl increase), and the risk is consistent in subgroup analyses and have a dose-response relationship.

Conclusions

Hyperuricemia may modestly increase the risk of hypertension incidence, consistent with a dose-response relationship.     

Impact of elevated uric acid on ventricular remodeling in infarcted rats with experimental hyperuricemia

Hyperuricemia is associated with cardiovascular disease, but it is usually considered a marker rather than a risk factor. Previous studies using uric acid-lowering drugs in normouricemic animals are not suitable to answer the effect of hyperuricemia on ventricular remodeling after myocardial infarction. The purpose of this study was to determine whether hyperuricemia adversely affects ventricular remodeling in infarcted rats with elevated uric acid. Male Wistar rats aged 8 wk were randomly assigned into either vehicle, oxonic acid, oxonic acid + allopurinol, oxonic acid + benzbromarone, oxonic acid + ABT-627, or oxonic acid + tempol for 4 wk starting 24 h after ligation. Postinfarction was associated with increased oxidant production, as measured by myocardial superoxide, isoprostane, xanthine oxidase activity, and dihydroethidium staining. Compared with normouricemic infarcted rats, hyperuricemic infarcted rats had a significant increase of superoxide production (1.7×) and endothelin-1 protein (1.2×) and mRNA (1.4×) expression, which was associated with increased left ventricular dysfunction and enhanced myocardial hypertrophy and fibrosis. These changes were all prevented by treatment with allopurinol. For similar levels of urate lowering, the uricosuric agent benzbromarone had no effect on ventricular remodeling. In spite of equivalent hyperuricemia, the ability of both ABT-627 and tempol to attenuate ventricular remodeling suggested involvement of endothelin-1 and redox pathways. Hyperuricemia is associated with unfavorable ventricular remodeling probably through a superoxide and endothelin-1-dependent pathway. Uric acid lowering without inhibition of superoxide and endothelin-1 may not have an effect on remodeling. Chronic administration of allopurinol, ABT-627, and tempol is associated with attenuated ventricular remodeling.     

The association of uric acid with glucose and lipids in general population: Croatian cross-sectional study

Hyperuricemia may have an important role in metabolic syndrome, cardiovascular diseases and stroke. Elevated serum uric acid concentration has been shown to be the strong predictor of cardiovascular mortality in several recently published studies. Our aim was to determine the prevalence of hyperuricemia in general Croatian population and to investigate the association of serum uric acid with glucose and lipids. This was a retrospective cross-sectional study on 6,476 consecutive adults. Prevalence of hyperuricemia was 13.9% in general population and it was significantly higher in males, than in females (26% vs. 6%; p < 0.001). Median uric acid concentration was higher in males than in females (343 vs. 238 micromol/L; p < 0.001). Age, glucose and lipid parameters did not correlate with uric acid. In hyperuricemic subjects, increased concentrations of glucose (33.1% vs. 13.1%; p < 0.001), triglycerides (46.9% vs. 17.6%; p < 0.001), total cholesterol (69.6% vs. 51.9%; p < 0.001), LDL-cholesterol (64.5% vs. 46.4%; p < 0.001) and decreased concentration of HDL-cholesterol (24.3% vs. 13.0%; p < 0.001) were more prevalent than in subjects with normal serum concentrations of uric acid. Hyperuricemia is highly prevalent in Croatian general population and it aggregates with hyperglycemia and dyslipidemia.     

Screening and Characterization of Purine Nucleoside Degrading Lactic Acid Bacteria Isolated from Chinese Sauerkraut and Evaluation of the Serum Uric Acid Lowering Effect in Hyperuricemic Rats

Hyperuricemia is well known as the cause of gout. In recent years, it has also been recognized as a risk factor for arteriosclerosis, cerebrovascular and cardiovascular diseases, and nephropathy in diabetic patients. Foods high in purine compounds are more potent in exacerbating hyperuricemia. Therefore, the development of probiotics that efficiently degrade purine compounds is a promising potential therapy for the prevention of hyperuricemia. In this study, fifty-five lactic acid bacteria isolated from Chinese sauerkraut were evaluated for the ability to degrade inosine and guanosine, the two key intermediates in purine metabolism. After a preliminary screening based on HPLC, three candidate strains with the highest nucleoside degrading rates were selected for further characterization. The tested biological characteristics of candidate strains included acid tolerance, bile tolerance, anti-pathogenic bacteria activity, cell adhesion ability, resistance to antibiotics and the ability to produce hydrogen peroxide. Among the selected strains, DM9218 showed the best probiotic potential compared with other strains despite its poor bile resistance. Analysis of 16S rRNA sequences showed that DM9218 has the highest similarity (99%) to Lactobacillus plantarum WCFS1. The acclimated strain DM9218-A showed better resistance to 0.3% bile salt, and its survival in gastrointestinal tract of rats was proven by PCR-DGGE. Furthermore, the effects of DM9218-A in a hyperuricemia rat model were evaluated. The level of serum uric acid in hyperuricemic rat can be efficiently reduced by the intragastric administration of DM9218-A (P<0.05). The preventive treatment of DM9218-A caused a greater reduction in serum uric acid concentration in hyperuricemic rats than the later treatment (P<0.05). Our results suggest that DM9218-A may be a promising candidate as an adjunctive treatment in patients with hyperuricemia during the onset period of disease. DM9218-A also has potential as a probiotic in the prevention of hyperuricemia in the normal population.     

高龄老年高血压患者高尿酸血症相关因素分析

目的分析高龄老年高血压患者高尿酸血症相关因素,探讨老年高血压与高尿酸血症之间的相关性。方法选择2015年6~12月收治的高龄老年高血压患者50例为观察组,同期选择50例健康体检的老年志愿者为对照组,观察两组血尿酸水平并进行比较分析。结果观察组高龄老年高血压患者并发高尿酸血症27例,发生率54.00%;对照组未检出高尿酸血症。两组血尿酸水平比较,差异具有统计学意义(P0.05);而且观察组TC、TG、LDL-C、HDL-C各指标均明显高于对照组,差异具有统计学意义(P0.05)。结论高龄老年高血压病与高尿酸血症密切相关,高尿酸血症也是导致高龄老年人心血管疾病的危险因素之一,临床需引起重视。