Weinberg J Brice, Lang Thomas, Wilkinson William E, Pisetsky David S, St Clair E William
Veterans Affairs Medical Center, 508 Fulton Street, Durham, NC 27705, USA.
Arthritis Res Ther. 2006;8(5):R140. doi: 10.1186/ar2030.
Nitric oxide (NO) may play important roles in rheumatoid arthritis (RA). RA is an inflammatory disease involving joints and other systems including salivary glands. To assess NO production in RA patients, we compared levels of serum, urine, and salivary nitrite and nitrate (NOx) in patients with RA and normal subjects, and we examined the relationships of these measures to disease activity. Serum, urine, and NOx levels as well as renal creatinine, NOx clearance and fractional excretion rates were compared in 25 RA patients and 20 age- and gender-matched healthy controls. Subjects were hospitalized for 3 days and placed on a NOx restricted diet. NOx was assayed using nitrate reductase and the Griess reagent. RA activity was assessed using standard clinical and laboratory measures. While consuming a restricted diet for 3 days to eliminate the effects of oral intake of NOx, 24 hour urinary NOx excretion decreased in both RA patients and healthy controls. Urine NOx levels at all time points were not significantly different between RA patients and normal subjects. Serum NOx levels also decreased during the 3 days of NOx restriction, but RA patients had higher serum NOx levels at all time points compared with the control group. Likewise, serum NOx/creatinine ratios were higher in RA patients than in controls. Although basal salivary flow rate and tear flow were lower in RA patients, salivary NOx levels did not differ between normal and RA subjects. While renal creatinine clearance was not different between the two groups, we found that RA patients had lower renal NOx clearance and lower renal NOx fractional excretion. After correction of p values for multiple comparisons, there were no significant relationships for the RA group between measures of disease activity and the urinary NOx, serum NOx, or urinary NOx clearance. Despite interest in the use of NO as a marker of disease activity, alterations in renal NOx clearance and fractional excretion in RA make it difficult to assess in vivo NO production even with strict dietary restriction of NOx intake.
一氧化氮（NO）可能在类风湿关节炎（RA）中发挥重要作用。RA是一种涉及关节及包括唾液腺在内的其他系统的炎症性疾病。为评估RA患者体内NO的生成情况，我们比较了RA患者与正常受试者血清、尿液及唾液中亚硝酸盐和硝酸盐（NOx）的水平，并研究了这些指标与疾病活动度之间的关系。比较了25例RA患者及20例年龄和性别匹配的健康对照者的血清、尿液、NOx水平以及肾肌酐、NOx清除率和排泄分数。受试者住院3天并采用限制NOx摄入的饮食。使用硝酸还原酶和格里斯试剂检测NOx。采用标准临床和实验室指标评估RA活动度。在食用限制饮食3天以消除口服摄入NOx的影响后，RA患者和健康对照者的24小时尿NOx排泄量均下降。RA患者和正常受试者在所有时间点的尿NOx水平均无显著差异。在限制NOx摄入的3天内，血清NOx水平也下降，但与对照组相比，RA患者在所有时间点的血清NOx水平均较高。同样，RA患者的血清NOx/肌酐比值高于对照组。尽管RA患者的基础唾液流速和泪液流速较低，但正常受试者与RA受试者的唾液NOx水平并无差异。虽然两组之间的肾肌酐清除率无差异，但我们发现RA患者的肾NOx清除率较低，肾NOx排泄分数也较低。在对多重比较的p值进行校正后，RA组的疾病活动度指标与尿NOx、血清NOx或尿NOx清除率之间无显著相关性。尽管人们对将NO用作疾病活动度标志物感兴趣，但RA患者肾NOx清除率和排泄分数的改变使得即使严格限制NOx摄入，也难以评估体内NO的生成情况。
