运动调控尿酸的作用机制

背景：体内尿酸积累过多会导致高尿酸血症和痛风等疾病,是心血管和肾功能障碍的危险因素。国内外多个运动医学组织机构都倡导制定运动处方来防治慢性疾病,然而在预防和治疗高尿酸血症的实践中此方法尚未得到有效开展。目的：以综述高尿酸血症形成和运动对尿酸的调控及相关机制为基础,凝练出适合大众化运动预防和辅助治疗高尿酸血症的方案,提出不同高尿酸血症阶段患者运动时的注意事项。方法：以“尿酸,痛风,有氧运动,力量训练,高强度间歇训练,肥胖”为中文检索词,以“uric acid,gout,aerobic exercise,strength training,high-intensity interval training,obesity”为英文检索词,分别检索PubMed数据库和中国知网数据库,搜寻各数据库建库至2023年10月发表的所有研究。通过阅读文题和摘要进行初步筛选,排除重复性研究及内容不相关的文献,最后纳入64篇文献进行综述。结果与结论：高尿酸血症的形成由肝脏合成尿酸过多、肾脏肾外排泄不足或二者共同导致。运动可通过调节抗氧化酶活性、尿酸排泄蛋白的表达、脂代谢途径来改善体内的尿酸水平,有氧运动、力量...     

高尿酸血症与血栓形成的关系

高尿酸血症又称痛风,是一组嘌呤代谢紊乱所致的疾病,其临床特点为高尿酸血症及由此而引起的痛风性急性关节炎反复发作、痛风石沉积、痛风石性慢性关节炎和关节畸形,常累及肾脏引起慢性间质性肾炎和尿酸肾结石形成.随着人们生活水平的不断提高,各种与生活习惯有关的疾病随之增加.近年来的研究证实,高尿酸血症除与痛风有关外,也能促进动脉硬化的发生、发展,从而成为血栓形成的危险因素,常常与肥胖、高脂血症、高血压、糖尿病伴随出现.本文对高尿酸血症的人群进行流行病学调查,探讨高尿酸血症与血栓形成的关系.     

高尿酸血症的分子遗传学研究进展

高尿酸血症（HUA）是一种涉及多基因遗传变异的疾病。血尿酸稳态由尿酸生成和排泄共同调节维持。高尿酸血症患病率逐年升高,且与代谢综合征密切关联,因此对其发病机制研究也愈受重视。最近研究发现,嘌呤代谢过程中关键酶次黄嘌呤鸟嘌呤磷酸核糖转移酶（HPRT）及磷酸核糖焦磷酸合成酶（PRS）基因遗传缺陷和肾脏尿酸盐转运体系中的尿酸盐阴离子交换体（URAT1）、葡萄糖转运体9（GLU9）、三磷酸腺苷结合盒转运蛋白G2（ABCG2）、尿调节素（UMOD）和含PDZ结构域蛋白1（PDZK1）基因变异可导致尿酸稳态失衡而致高尿酸血症,但具体分子机制尚未完全清楚。本文主要对近几年高尿酸血症发病机制的分子遗传学研究进展进行综述。     

高尿酸血症治疗的研究进展

高尿酸血症是由于体内嘌呤代谢紊乱导致的代谢性疾病。我国高尿酸血症患病率高达13.3%。高尿酸血症不仅是痛风最重要的危险因素,也与多个重要靶器官损害密切相关。目前临床上使用的降尿酸药物存在一定的副作用且大多治疗成本较高。营养素是维持人体基本功能必不可少的物质。研究发现,叶酸、维生素C、血清磷、血清镁等营养素与高尿酸血症发生风险呈负相关,提示营养治疗可能是防治高尿酸血症的潜在策略。本文对高尿酸血症的发病机制、并发症及治疗进展进行综述。     

鹌鹑高尿酸血症模型建立初探

高尿酸血症侵犯各个种族 ,广泛见于世界各地。随着人类饮食结构的变化 ,食物中蛋白质增高 ,促使了高尿酸血症导致痛风病的增加。因而为给临床研制和评估治疗痛风药物及探讨高尿酸血症的发病机理 ,提供一个接近于人类尿酸代谢的高尿酸血症动物模型尤显重要。为此 ,我们以鹌鹑作为研究对象 ,试图寻找尿酸代谢途径与人类较一致的动物塑造高尿酸血症的模型。材　料　和　方　法1　材料1 1　实验对象　迪法克品系鹌鹑 ,雄性 ,体重 170 -190ｇ ,北京市种禽公司鹌鹑场提供 ,购来后在本室饲养 3- 5ｄ后用于实验。1 2　药品和试剂　尿酸 (ｕｒｉｃａ…     

钠依赖性磷酸转运蛋白在痛风/高尿酸血症中的研究进展

钠依赖性磷酸转运蛋白由溶质载体家族17基因编码,编码基因位于6号染色体上,是人体重要的以有机阴离子为底物的转运蛋白,在肾脏等组织中表达。其中钠依赖性磷酸转运蛋白1、3和4有转运尿酸的功能,功能异常会导致尿酸排泄减少,从而引起高尿酸血症,甚至诱发痛风。     

高尿酸血症模型的建立及降尿酸药物的研究进展

正高尿酸血症(hyperuricemia)指血清尿酸(uricacid)浓度男性高于416.4μmol/L(7.0 mg/d L),女性高于356.9μmol/L(6.0 mg/d L)[1]。高尿酸血症的发生可能是由于尿酸生成过多和(或)肾脏、肠道排泄减少导致血清尿酸浓度过度增加[2-4]。流行病学研究显示,高尿酸血症已成为一个严重的公共卫生问题,2017年的数据显示,我国高尿酸血症患病率为13.0%,其中男性为18.5%,女性为8.0%[5]。     

高尿酸血症动物模型研究进展

构建合理的动物模型是研究高尿酸血症致病机制的重要环节.目前高尿酸血症动物模型复制方法多样,常用的造模动物为禽类和啮齿类,主要造模方法有补充尿酸前体物质次黄嘌呤、补充外源性尿酸,使用氧嗪酸抑制尿酸酶活性、腺嘌呤抑制尿酸排泄.相对成熟的造模方法为尿酸和氧嗪酸联合使用.高尿酸血症动物模型尚缺乏公认评价指标,理想的模型仍需进一...     

男性痛风患者脂代谢紊乱的相关性研究

目的 通过分析男性痛风患者与高尿酸血症患者及正常人脂代谢指标的差异,探索尿酸水平与脂蛋白水平的相关性.方法 收集2018年至2020年首都医科大学附属北京世纪坛医院风湿科痛风患者655例为实验组、高尿酸血症患者732例和体检中心健康者646例为对照组,4h内检测尿酸、三酰甘油、总胆固醇、高密度脂蛋白、低密度脂蛋白等脂代谢指标,并进行数据处理和统计分析.结果(1)痛风患者及高尿酸血症患者的SUA、TG、LDL-C均高于健康体检者,而HDL-C低于健康体检者,且差异均有统计学意义(P<0.05);(2)痛风患者的CHO水平显著高于高尿酸血症患者,差异有统计学意义(t=2.33,P=0.02);(3)痛风组中SUA与CHO、TG、LDL-C水平呈正相关(r=0.095、0.129、0.116,P<0.05),与HDL-C呈负相关(r=-0.139,P<0.05);高尿酸血症组中,SUA与TG呈正相关(r=0.110,P<0.05),与HDL-C呈负相关(r=-0.146,P<0.05);正常对照组中,SUA与CHO和TG呈正相关(r=0.103,0.137,P<0.05).结论 男性患者间痛风可伴有脂代谢紊乱,而尿酸水平的升高可能与脂代谢紊乱相互影响.     

ABCG2 基因rs3114018单核苷酸多态性与武陵山地区痛风及高尿酸血症的相关性研究

目的：探讨三磷酸腺苷结合盒转运蛋白 G2 基因(ABCG2) rs3114018位点与武陵山地区原发性痛风和高尿酸血症的相关性。方法：采用Hi-SNP结合多重PCR技术和高通量测序技术,对159例原发性痛风患者、188例高尿酸血症患者和106例健康对照者的ABCG2 rs3114018位点进行基因分型,并分析不同等位基因或基因型与原发性痛风、高尿酸血症易感性的关系。结果：痛风组基因型频率与正常组相比差异具有统计学显著统计学意义（P<0.001),Logistic回归分析显示,基因型CC和C等位基因均是痛风的易感因素(OR=5.861,95%CI:2.239~15.340,P<0.001;OR=2.461,95%CI:1.671~3.622,P<0.001）;高尿酸血症组基因型频率与正常组相比没有显著差异（P>0.05),该位点多态与高尿酸血症没有相关性（P>0.05）;痛风组与高尿酸血症组相比,基因型频率具有统计学差异（P<0.001),基因型CC和C等位基因分别使痛风的发生风险增加了4.131倍和1.994倍。结论：ABCG2 rs3114018位点单核苷酸多态性可能与武陵山地区原发性痛风的发病相关,等位基因C可能是原发性痛风发病的危险因素,携带CC基因型的个体可能更容易患痛风;该位点多态性与高尿酸血症没有显著相关性。     

Renal regulation of plasma total antioxidant capacity

Hyperuricemia has been labeled both a risk factor and marker for cardiovascular pathology in addition to being associated with gout and kidney disease. Uric acid in vitro acts as a potent antioxidant capable of scavenging hydroxy radicals and peroxynitrite and reacting with nitric oxide. Some clinical studies have provided evidence that, in vivo, uric acid is oxidized under conditions associated with high oxidant stress and may spare other antioxidants such as ascorbic acid. The plasma level of uric acid is controlled by the rates of production and excretion or degradation of uric acid. Under most circumstances, it is the renal clearance of uric acid which primarily determines the plasma concentration. Many factors of exogenous and endogenous origin can influence renal tubular absorption and secretion of uric acid. We suggest that renal urate clearance is not haphazard but regulated by an unknown signal that is issued in response to the level of oxidative stress. Since much cardiovascular pathology is now believed to have an inflammatory component and is associated with enhanced production of free radicals, the accompanying hyperuricemia may be viewed as a compensatory response of potential benefit.     

A case of familial juvenile hyperuricemic nephropathy with novel uromodulin gene mutation, a novel heterozygous missense mutation in Korea

Familial Juvenile hyperuricemic nephropathy (FJHN, OMIM #162000) is a rare autosomal dominant disorder characterized by hyperuricemia with renal uric acid under-excretion, gout and chronic kidney disease. In most but not all families with FJHN, genetic studies have revealed mutations in the uromodulin (UMOD) gene located on chromosome 16p11-p13. We here described a novel heterozygous missense mutation (c.1382C>A causing p.Ala461Glu) in an affected 16-year-old male with hyperuricemia, gout and chronic kidney disease. His father was also affected and the UMOD mutation was found to segregate with the disease. There has been only one case report of Korean family with FJHN, which has not been diagnosed by genetic study. This is the first report of genetically diagnosed FJHN in Korea.     

Association of renal manifestations with serum uric acid in Korean adults with normal uric acid levels

Several studies have reported that hyperuricemia is associated with the development of hypertension and cardiovascular disease. Increasing evidences also suggest that hyperuricemia may have a pathogenic role in the progression of renal disease. Paradoxically, uric acid is also widely accepted to have antioxidant activity in experimental studies. We aimed to investigate the association between glomerular filtration rate (GFR) and uric acid in healthy individuals with a normal serum level of uric acid. We examined renal function determined by GFR and uric acid in 3,376 subjects (1,896 men; 1,480 women; aged 20-80 yr) who underwent medical examinations at Gangnam Severance Hospital from November 2006 to June 2007. Determinants for renal function and uric acid levels were also investigated. In both men and women, GFR was negatively correlated with systolic and diastolic blood pressures, fasting plasma glucose, total cholesterol, uric acid, log transformed C reactive protein, and log transformed triglycerides. In multivariate regression analysis, total uric acid was found to be an independent factor associated with estimated GFR in both men and women. This result suggests that uric acid appears to contribute to renal impairment in subjects with normal serum level of uric acid.     

膝关节液pH值与痛风结晶的形成

背景：引起痛风结晶析出的原因除了尿酸盐浓度升高之外还应有其他的影响因素。 目的：探讨膝关节液pH值在痛风结晶形成中的意义。 方法：选择2008-08/2010-12桂林医学院附属医院脊柱骨病外科因膝关节疾病就诊的患者40例,分为2组,实验组：关节镜检见关节内白垩样结晶沉积者。对照组：关节镜检关节内无明显白垩样结晶形成。其中实验组膝关节液25份,对照组膝关节液15份。检测并比较两组患者的关节液pH值。 结果与结论：实验组pH值7.8±0.2,对照组pH值8.5±0.3。镜检有痛风结晶形成的膝关节液pH值较无痛风结晶形成的膝关节液pH值明显偏低,差异有显著性意义(P < 0.001)。提示有痛风结晶形成的膝关节液pH值较无痛风结晶形成的膝关节液pH值明显偏酸性,膝关节液pH值降低是痛风结晶析出的危险因素之一。     

Aronia melanocarpa ameliorates gout and hyperuricemia in animal models

Aronia melanocarpa fruit (AM) strongly suppressed ankle swelling in rats with acute gout and reduced the levels of uric acid and xanthine oxidase (XO) in mice with hyperuricemia. AM reduced the inflammatory cell count and increased the ankle joint space, and suppressed the levels of interleukin (IL)-1β, IL-10, monocyte chemoattractant protein-1 and tumour necrosis factor-α in the serum of the rats with acute gout. In the mice with hyperuricemia, AM significantly reduced the serum levels of uric acid, blood urea nitrogen, and creatinine. 8-day administration of AM resulted in enhancements in the levels of glutathione peroxidase, superoxide dismutase and catalase and a reduction in the level of malondialdehyde in the serum of mice. All data suggested that the potential therapeutic effects of AM on gout are probably due to the regulation of pro- and anti-inflammatory cytokines and the suppression of XO activity via modulation of the oxidative stress status.     

脊柱椎间盘退变与高尿酸血症的相关性

背景:高尿酸血症是常见的代谢性疾病,高尿酸血症患者以尿酸结晶形成导致痛风为主要临床表现。既往研究仅报道了尿酸结晶会导致脊柱椎间盘的退变,但关于高尿酸血症与脊柱椎间盘退变的相关性研究较少。目的:回顾性分析高尿酸血症患者脊柱椎间盘的退变特点以及血尿酸浓度与脊柱椎间盘退变的相关性。方法:回顾性分析2021年1月至2022年12月在西南医科大学附属医院骨科就诊并被诊断为脊柱椎间盘退变的所有患者,纳入97例高尿酸血症患者作为高尿酸血症组,然后根据性别、年龄按照1∶2进行匹配,将194例非高尿酸血症患者作为对照组。收集两组患者的血尿酸检验结果,并在全脊柱MRI图像上对两组患者的椎间盘退变程度进行Pfirrmann评分。比较两组患者椎间盘退变程度的差异,分析血尿酸浓度与椎间盘退变程度的相关性。结果与结论:①高尿酸血症组的椎间盘退变程度Pfirrmann评分大于对照组,且高尿酸血症组的椎间盘退变总数大于对照组,差异均有显著性意义(P<0.05);②Spearman相关分析显示,在高尿酸血症组内的多个节段,男性患者的椎间盘退变程度与血尿酸浓度呈正相关(C_(3/4):r=0.317,C_(4/5):r=0.333,C_(5/6):r=0.309,L_(2/3):r=0.443;P<0.05);女性患者的椎间盘退变程度也与血尿酸浓度呈正相关(C_(3/4):r=0.354,C_(4/5):r=0.388,C_(6/7):r=0.312,T_(7/8):r=0.282,T_(9/10):r=0.305,T_(11/12):r=0.277,L_(4/5):r=0.319,L_(5)-S_(1):r=0.367,P<0.05);③在对照组中,男性和女性患者的椎间盘退变程度与血尿酸浓度无明显相关性(P>0.05);④结果提示:在高尿酸血症患者中,血尿酸浓度越高,椎间盘退变程度越严重。因此,高尿酸血症是导致椎间盘退变的危险因素之一。     

X-linkage does not account for the absence of father-son similarity in plasma uric acid concentrations

Plasma uric acid concentration aggregates in families, and this similarity has been suggested to be due, in part, to multiple shared genes. Men have higher plasma uric acid concentrations than women and are affected with gout nine times more frequently. Rare forms of hyperuricemia and gout are due to mutations of X-linked genes (HPRT1 and PRPS1). Given these observations, we tested the hypothesis that normal variation in plasma uric acid levels would display a pattern of familial similarity consistent with X-linkage in 892 individuals from 196 obese but otherwise healthy families. As predicted by X-linked inheritance, fathers and sons showed no resemblance in plasma uric acid concentration (r = 0.013, NS), while all other pairings showed moderate-to-strong familial resemblance (ranging from 0.167, P < 0.01, parent-offspring to 0.415, sister-sister, P < 0.01). We then tested the hypothesis that loci along the X chromosome would influence plasma uric acid concentration. We conducted both single-point and multipoint linkage analyses using 17 X-linked markers spaced at approximately 9 cm intervals to determine whether allele sharing among sibs was related to sib similarity in plasma uric acid concentrations (n = 1,100 sib pairs). We found no regions of the X chromosome that cosegregated with plasma uric acid concentrations (P > 0.05). We conclude that variation in genes on the X chromosome contribute little to normal variation in plasma uric acid concentrations.     

肾移植后的尿酸性肾石病

背景：高尿酸血症是肾移植后常见的并发症之一,其引起的尿酸性肾石病如果治疗不及时可以造成移植肾肾后性失功。 目的：探讨肾移植后尿酸性肾石病的诊断和治疗方案。 方法：回顾性总结19例肾移植后发生尿酸性肾石病梗阻患者的临床资料,入院时均伴高尿酸血症,8例患者手术切开取石并行输尿管-膀胱再吻合术,11例患者行药物保守治疗。 结果与结论：16例患者为移植输尿管下段结石,2例为移植肾肾盂结石并肾盂积水,1例为移植肾重度积水并输尿管全段结石。18例患者治疗后移植肾功能、尿量恢复正常;1例患者造成移植肾失功能,切除移植肾。提示对于肾移植后血尿酸升高患者应尽早应用药物保守治疗,一旦保守治疗无效应及时采取手术方式,减少肾后性原因引起的移植肾失功。     

Rasburicase represents a new tool for hyperuricemia in tumor lysis syndrome and in gout

Hyperuricemia is a feature of several pathologies and requires an appropriate and often early treatment, owing to the severe consequences that it may cause. A rapid and massive raise of uric acid, during tumor lysis syndrome (TLS), and also a lower and chronic hyperuricemia, as in gout, mainly damage the kidney. To prevent or treat these consequences, a new therapeutic option is represented by rasburicase, a recombinant form of an enzyme, urate oxidase. This enzyme converts hypoxanthine and xanthine into allantoin, a more soluble molecule, easily cleared by kidney. The several types of urate oxidase have followed each other, with progressive reduction of adverse reactions. The most important among them are allergenicity and the development of antibodies which compromise their effectiveness. Nevertheless, a limit of rasburicase's use remains its cost, which obliges to a judicious choice to prevent TLS in high risk patients with cancer and in case of allergy or impossibility to take allopurinol orally both in TLS and in gout. A large body of evidence confirms the efficacy and safety of rasburicase, even in comparison to the standard drugs used in the aforementioned pathologies.