正常范围血清尿酸水平与膝骨关节炎症状及结构改变的相关性

卞福勤; 徐建华; 王康; 阮光峰; 任家乐; 常冰茹; 丁长海

doi:10.16462/j.cnki.zhjbkz.2019.05.022

正常范围血清尿酸水平与膝骨关节炎症状及结构改变的相关性

doi: 10.16462/j.cnki.zhjbkz.2019.05.022

卞福勤¹,
徐建华¹,
王康¹,
阮光峰¹,
任家乐¹,
常冰茹¹,
丁长海^{1, 2, 3, ,}

1.
230032 合肥, 安徽医科大学第一附属医院风湿免疫科
2.
7000 塔斯马尼亚霍巴特, 澳大利亚塔斯马尼亚大学孟席斯医学研究所
3.
510282 广州, 南方医科大学珠江医院临床研究中心

基金项目:

国家自然科学基金 81172865

详细信息

通讯作者:
丁长海, E-mail: Changhai.Ding@utas.edu.au

中图分类号: R181.22
计量
- 文章访问数: 284
- HTML全文浏览量: 148
- PDF下载量: 13
- 被引次数: 0
出版历程
- 收稿日期: 2018-10-29
- 修回日期: 2019-01-22
- 刊出日期: 2019-05-10

Associations between normal serum levels of uric acid and knee symptoms, joint structures in patients with knee osteoarthritis

1.
Department of Rheumatology and Immunology, Arthritis Research Institute, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230032, China
2.
Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania 7000, Australia
3.
Clinical Research Centre, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, China

Funds:

The National Natural Science Foundation of China 81172865

More Information

Corresponding author: DING Chang-hai, E-mail: Changhai.Ding@utas.edu.au

摘要

摘要: 目的探讨膝骨关节炎(osteoarthritis，OA)患者正常范围血清尿酸(uric acid，UA)水平与膝关节症状、结构改变之间的相关性。方法收集205例膝OA患者，根据纳入及排除标准，最终122例OA患者纳入研究，调查患者一般情况，WOMAC骨关节炎指数(western ontario and mcMaster universities osteoarthritis index，WOMAC)评分评估膝关节症状严重程度，Kellgren-Lawrenc(K-L)分级评估膝关节放射学严重程度，在磁共振成像(magnetic resonance imaging，MRI)上利用Osirix软件测量关节结构改变，过氧化物酶法测定血清UA水平，选取正常范围UA纳入研究，分析UA水平与膝关节症状、结构改变之间的关系。结果研究发现，以UA中位数(263 μmol/L)分组进行组间比较，与UA ≥ 263 μmol/L组相比，UA < 263 μmol/L组患者的身高、体重较小，女性较多，而K-L分级≥ 2的比例较低；调整性别、年龄及体质指数后，UA水平与WOMAC总分(β=-16.15，P=0.018)、WOMAC疼痛(β=-3.15，P=0.037)、WOMAC僵硬(β=-1.65，P=0.025)呈负相关；但UA水平与膝关节结构改变无明显相关性。结论在膝OA患者中，正常UA水平与关节症状严重程度呈负相关，提示正常水平UA可能对OA关节症状具有保护作用。
- 骨关节炎 /
- 尿酸 /
- 磁共振成像
Abstract: Objective To investigate the associations between normal serum uric acid (UA) levels and knee symptoms and structural changes in patients with knee osteoarthritis (OA). Methods A total of 205 patients with knee OA were enrolled. According to the inclusion and exclusion criteria, 122 patients with OA were included in the study. The general condition of patients were investingated. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score was used to assess severity of the knee joint symptoms. The Kellgren-Lawrence (K-L) grading system was used to assess radiological severity of the knee joint. Osirix software was used to assess changes of knee structure in magnetic resonance imaging (MRI). Peroxidase method was used to measure the serum levels of uric acid. Patients with normal range of uric acid were included in the study. Results The patients with lower levels of UA (split at the median level, 263 μmol/L) had a higher proportion of women, lower height, weight and lower proportions of K-L grade ≥ 2. After adjustment for sex, age and body mass index, serum UA was negatively associated with total WOMAC scores (β=-16.15, P=0.018), WOMAC pain (β=-3.15, P=0.037), and WOMAC stiffness (β=-1.65, P=0.025). However, there were no significant associations between serum UA levels and knee joint structure changes. Conclusions In OA patients with normal serum UA, serum UA is negatively associated with the severity of joint symptoms, suggesting that UA within normal range may play a protective role in OA symptoms.
- Osteoarthritis /
- Uric acid /
- Magnetic resonance imaging

HTML全文

表 1 膝OA患者的一般特征(以尿酸中位数分组)

Table 1. Characteristics of patients with knee OA (split by median level of UA)

项目	尿酸＜中位数(n=61)	尿酸≥中位数(n=61)	t/χ²/Z值	P值
年龄^a	54.17±7.46	56.06±8.58	-1.301	0.195
女性(%)^b	95.00	83.90	6.438	0.011
身高(cm)^a	157.05±4.57	159.48±6.90	-2.295	0.024
体重(kg)^a	62.04±8.63	66.97±11.29	-2.699	0.008
BMI(kg/m²)^a	25.13±3.17	26.34±4.31	-1.753	0.082
WOMAC总分^a	108.58±42.04	98.85±42.10	1.277	0.204
疼痛^a	23.92±9.23	21.98±8.92	1.172	0.244
平地行走时^a	4.58±2.17	4.18±2.29	1.004	0.317
上下楼梯时^a	6.47±2.05	6.24±2.34	0.563	0.574
晚上睡眠时^a	4.37±2.69	3.77±2.54	1.252	0.213
坐着或躺着时^a	3.58±2.40	3.21±2.07	0.921	0.359
站立时^a	4.50±2.27	4.19±2.19	0.759	0.449
僵硬^a	7.85±4.56	6.93±4.09	1.164	0.247
晨起时^a	3.78±2.66	3.45±2.30	0.737	0.463
白天时^a	3.90±2.50	3.39±2.22	1.199	0.233
功能障碍^a	76.82±31.22	71.56±29.85	0.947	0.345
K-L分级≥2%^b	62.7%	77.2%	4.667	0.031
总软骨体积(cm³)^a	4.16±0.90	4.38±1.06	-1.166	0.246
总软骨缺损^c	11 (10, 12)	10 (9, 14)	-1.094	0.274
总BMLs^c	2 (1, 5)	2 (1, 4)	-1.252	0.211
IPFP信号强度改变≥2%^b	28.3%	40%	3.209	0.073
注：^a表示t检验；^b表示χ²检验；^c表示Mann-Whitney U检验。

下载: 导出CSV

表 2 OA患者尿酸与膝关节症状的相关性

Table 2. Association between UA and knee joint symptoms in patients with knee OA

项目	单因素分析		多因素分析^a
项目	β (95%CI)值	P值	β (95%CI)值	P值
WOMAC总分	-12.43(-25.56~0.71)	0.063	-16.15(-29.45~-2.85)	0.018
疼痛	-1.97(-4.85~0.91)	0.177	-3.15(-6.11~-0.20)	0.037
平地行走时	-0.29(-0.99~0.41)	0.417	-0.53(-1.25~0.20)	0.155
上下楼梯时	-0.24(-0.93~0.45)	0.494	-0.26(-0.99~0.47)	0.482
晚上睡眠时	-0.56(-1.38~0.26)	0.180	-0.88(-1.72~-0.04)	0.040
坐着或躺着时	-0.61(-1.31~0.09)	0.086	-0.81(-1.53~-0.09)	0.027
站立时	-0.28(-0.98~0.42)	0.426	-0.53(-1.25~0.19)	0.149
僵硬	-1.24(-2.61~0.12)	0.073	-1.65(-3.09~-0.21)	0.025
晨起时	-0.45(-1.23~0.33)	0.253	-0.57(-1.39~0.26)	0.174
白天时	-0.74(-1.48~-0.01)	0.048	-0.97(-1.74~-0.20)	0.014
功能障碍	-7.12(-16.77~2.53)	0.147	-9.68(-19.58~0.23)	0.055
注：^a表示调整因素为年龄、性别、BMI。

下载: 导出CSV

表 3 OA患者尿酸与膝关节结构改变的相关性

Table 3. Association between UA and knee joint structural changes in patients with knee OA

项目	单因素分析		多因素分析^a
项目	β (95%CI)值	P值	β (95%CI)值	P值
总软骨体积(cm³)	0.37 (0.05~0.69)	0.024	0.05 (-0.25~0.35)	0.744
K-L分级	1.28 (0.69~2.34)	0.431	1.20 (0.62~2.33)	0.585
总软骨缺损	0.72 (0.40~1.30)	0.279	0.76 (0.40~1.41)	0.379
总BMLs	0.84 (0.46~1.55)	0.584	0.83 (0.43~1.59)	0.570
IPFP信号强度改变	0.97 (0.51~1.84)	0.929	0.83 (0.41~1.68)	0.608
注：^a表示调整因素为年龄、性别、BMI。

下载: 导出CSV

参考文献(29)

[1]	蔡静玉, 韩卫雨, 丁长海. 骨关节炎的队列研究现状[J]. 中华疾病控制杂志, 2017, 21(6): 539-545. DOI: 10.16462/j.cnki.zhjbkz.2017.06.001. Cai JY, Han WY, Ding CH. Cohort study status of osteoarthritis[J]. Chin J Dis Control Prev, 2017, 21(6): 539-545. DOI: 10.16462/j.cnki.zhjbkz.2017.06.001.
[2]	朱晓玥, 沈俊杰, 桑灵丽, 等. 药物治疗骨关节炎的疗效比较: 网络Meta分析[J]. 中华疾病控制杂志, 2018, 22(4): 396-401. DOI: 10.16462/j.cnki.zhjbkz.2018.04.017. Zhu XY, Shen JJ, Sang LL, et al. Comparative effectiveness of oral pharmacotherapy in the treatment of osteoarthritis: network meta-analysis[J]. Chin J Dis Control Prev, 2018, 22(4): 396-401. DOI: 10.16462/j.cnki.zhjbkz.2018.04.017.
[3]	Richette P, Bardin T. Gout[J]. Lancet, 2010, 375(9711): 318-328. DOI: 10.1016/S0140-6736(09)60883-7.
[4]	Wu XW, Muzny DM, Lee CC, et al. Two independent mutational events in the loss of urate oxidase during hominoid evolution[J]. J Mol Evol, 1992, 34(1): 78-84. doi: 10.1007/BF00163854
[5]	Kratzer JT, Lanaspa MA, Murphy MN, et al. Evolutionary history and metabolic insights of ancient mammalian uricases[J]. Proc Natl Acad Sci USA, 2014, 111(10): 3763-3768. DOI: 10.1073/pnas.1320393111.
[6]	Zhuang C, Wang Y, Zhang Y, et al. Oxidative stress in osteoarthritis and antioxidant effect of polysaccharide from angelica sinensis[J]. Int J Biol Macromol, 2018, 115: 281-286. DOI: 10.1016/j.ijbiomac.2018.04.083.
[7]	Glantzounis GK, Tsimoyiannis EC, Kappas AM, et al. Uric acid and oxidative stress[J]. Curr Pharm Des, 2005, 11(32): 4145-4151. doi: 10.2174/138161205774913255
[8]	Altman R, Asch E, Bloch D, et al. Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association[J]. Arthritis Rheum, 1986, 29(8): 1039-1049. doi: 10.1002/art.1780290816
[9]	Peterfy CG, Guermazi A, Zaim S, et al. Whole-Organ Magnetic Resonance Imaging Score (WORMS) of the knee in osteoarthritis[J]. Osteoarthritis Cartilage, 2004, 12(3): 177-190. DOI: 10.1016/j.joca.2003.11.003.
[10]	Hunter DJ, Guermazi A, Lo GH, et al. Evolution of semi-quantitative whole joint assessment of knee OA: MOAKS (MRI Osteoarthritis Knee Score)[J]. Osteoarthritis Cartilage, 2011, 19(8): 990-1002. DOI: 10.1016/j.joca.2011.05.004.
[11]	Xu Q, Chen B, Wang Y, et al. The effectiveness of manual therapy for relieving pain, stiffness, and dysfunction in knee osteoarthritis: a systematic review and meta-analysis[J]. Pain Physician, 2017, 20(4): 229-243.
[12]	Neogi T. The epidemiology and impact of pain in osteoarthritis[J]. Osteoarthritis Cartilage, 2013, 21(9): 1145-1153. DOI: 10.1016/j.joca.2013.03.018.
[13]	Fiskum G, Rosenthal RE, Vereczki V, et al. Protection against ischemic brain injury by inhibition of mitochondrial oxidative stress[J]. J Bioenerg Biomembr, 2004, 36(4): 347-352. DOI: 10.1023/B:JOBB.0000041766.71376.81.
[14]	Hwang J, Kleinhenz DJ, Rupnow HL, et al. The PPARy ligand, rosiglitazone, reduces vascular oxidative stress and NADPH oxidase expression in diabetic mice[J]. Vascul Pharmacol, 2007, 46(6): 456-462. DOI: 10.1016/j.vph.2007.01.007.
[15]	Mishra R, Singh A, Chandra V, et al. A comparative analysis of serological parameters and oxidative stress in osteoarthritis and rheumatoid arthritis[J]. Rheumatol Int, 2012, 32(8): 2377-2382. DOI: 10.1007/s00296-011-1964-1.
[16]	Kyostio-Moore S, Bangari DS, Ewing P, et al. Local gene delivery of heme oxygenase-1 by adeno-associated virus into osteoarthritic mouse joints exhibiting synovial oxidative stress[J]. Osteoarthritis Cartilage, 2013, 21(2): 358-367. DOI: 10.1016/j.joca.2012.11.002.
[17]	Jeong CH, Joo SH. Downregulation of reactive oxygen species in apoptosis[J]. J Cancer Prev, 2016, 21(1): 13-20. DOI: 10.15430/JCP.2016.21.1.13.
[18]	Roberts JS, Yilmaz. Dangerous liaisons: caspase-11 and reactive oxygen species crosstalk in pathogen elimination[J]. Int J Mol Sci, 2015, 16(10): 23337-23354. DOI: 10.3390/ijms161023337.
[19]	Tetik S, Ahmad S, Alturfan AA, et al. Determination of oxidant stress in plasma of rheumatoid arthritis and primary osteoarthritis patients[J]. Indian J Biochem Biophys, 2010, 47(6): 353-358. http://www.ncbi.nlm.nih.gov/pubmed/21355418
[20]	Ames BN, Cathcart R, Schwiers E, et al. Uric acid provides an antioxidant defense in humans against oxidant-and radical-caused aging and cancer: a hypothesis[J]. Proc Natl Acad Sci USA, 1981, 78(11): 6858-6862. doi: 10.1073/pnas.78.11.6858
[21]	lvarez-Lario B, Macarrón-Vicente J. Uric acid and evolution[J]. Rheumatology(Oxford), 2010, 49(11): 2010-2015. DOI: 10.1093/rheumatology/keq204.
[22]	Pacher P, Beckman JS, Liaudet L. Nitric oxide and peroxynitrite in health and disease[J]. Physiol Rev, 2007, 87(1): 315-424. DOI: 10.1152/physrev.00029.2006.
[23]	Mazzetti I, Grigolo B, Pulsatelli L, et al. Differential roles of nitric oxide and oxygen radicals in chondrocytes affected by osteoarthritis and rheumatoid arthritis[J]. Clin Sci (Lond), 2001, 101(6): 593-599. doi: 10.1042/cs1010593
[24]	Zhou Y, Liu SQ, Yu L, et al. Berberine prevents nitric oxide-induced rat chondrocyte apoptosis and cartilage degeneration in a rat osteoarthritis model via AMPK and p38 MAPK signaling[J]. Apoptosis, 2015, 20(9): 1187-1199. DOI: 10.1007/s10495-015-1152-y.
[25]	Santoro A, Conde J, Scotece M, et al. Choosing the right chondrocyte cell line: focus on nitric oxide[J]. J Orthop Res, 2015, 33(12): 1784-1788. DOI: 10.1002/jor.22954.
[26]	Chhana A, Callon KE, Pool B, et al. The effects of monosodium urate monohydrate crystals on chondrocyte viability and function: implications for development of cartilage damage in gout[J]. J Rheumatol, 2013, 40(12): 2067-2074. DOI: 10.3899/jrheum.130708.
[27]	Muehleman C, Li J, Aigner T, et al. Association between crystals and cartilage degeneration in the ankle[J]. J Rheumatol, 2008, 35(6): 1108-1117. http://www.ncbi.nlm.nih.gov/pubmed/18412302
[28]	Liu R, Lioté F, Rose DM, et al. Proline-rich tyrosine kinase 2 and src kinase signaling transduce monosodium urate crystal-induced nitric oxide production and matrix metalloproteinase 3 expression in chondrocytes[J]. Arthritis Rheum, 2004, 50(1): 247-258. DOI: 10.1002/art.11486.
[29]	Yokose C, Chen M, Berhanu A, et al. Gout and osteoarthritis: associations, pathophysiology, and therapeutic implications[J]. Curr Rheumatol Rep, 2016, 18(10): 65. DOI: 10.1007/s11926-016-0613-9.

施引文献

资源附件(0)

访问统计

点击查看大图

项目	尿酸＜中位数(n=61)	尿酸≥中位数(n=61)	t/χ²/Z值	P值
年龄^a	54.17±7.46	56.06±8.58	-1.301	0.195
女性(%)^b	95.00	83.90	6.438	0.011
身高(cm)^a	157.05±4.57	159.48±6.90	-2.295	0.024
体重(kg)^a	62.04±8.63	66.97±11.29	-2.699	0.008
BMI(kg/m²)^a	25.13±3.17	26.34±4.31	-1.753	0.082
WOMAC总分^a	108.58±42.04	98.85±42.10	1.277	0.204
疼痛^a	23.92±9.23	21.98±8.92	1.172	0.244
平地行走时^a	4.58±2.17	4.18±2.29	1.004	0.317
上下楼梯时^a	6.47±2.05	6.24±2.34	0.563	0.574
晚上睡眠时^a	4.37±2.69	3.77±2.54	1.252	0.213
坐着或躺着时^a	3.58±2.40	3.21±2.07	0.921	0.359
站立时^a	4.50±2.27	4.19±2.19	0.759	0.449
僵硬^a	7.85±4.56	6.93±4.09	1.164	0.247
晨起时^a	3.78±2.66	3.45±2.30	0.737	0.463
白天时^a	3.90±2.50	3.39±2.22	1.199	0.233
功能障碍^a	76.82±31.22	71.56±29.85	0.947	0.345
K-L分级≥2%^b	62.7%	77.2%	4.667	0.031
总软骨体积(cm³)^a	4.16±0.90	4.38±1.06	-1.166	0.246
总软骨缺损^c	11 (10, 12)	10 (9, 14)	-1.094	0.274
总BMLs^c	2 (1, 5)	2 (1, 4)	-1.252	0.211
IPFP信号强度改变≥2%^b	28.3%	40%	3.209	0.073
注：^a表示t检验；^b表示χ²检验；^c表示Mann-Whitney U检验。

表(3)

计量

文章访问数: 284
HTML全文浏览量: 148
PDF下载量: 13
被引次数: 0

姓名
邮箱
手机号码
标题
留言内容
验证码

留言板

正常范围血清尿酸水平与膝骨关节炎症状及结构改变的相关性

doi: 10.16462/j.cnki.zhjbkz.2019.05.022

通讯作者:
丁长海, E-mail: Changhai.Ding@utas.edu.au

计量

Associations between normal serum levels of uric acid and knee symptoms, joint structures in patients with knee osteoarthritis

Corresponding author: DING Chang-hai, E-mail: Changhai.Ding@utas.edu.au

计量

目录

留言板

正常范围血清尿酸水平与膝骨关节炎症状及结构改变的相关性

doi: 10.16462/j.cnki.zhjbkz.2019.05.022

通讯作者: 丁长海, E-mail: Changhai.Ding@utas.edu.au

计量

出版历程

Associations between normal serum levels of uric acid and knee symptoms, joint structures in patients with knee osteoarthritis

Corresponding author: DING Chang-hai, E-mail: Changhai.Ding@utas.edu.au

计量

出版历程

目录

通讯作者:
丁长海, E-mail: Changhai.Ding@utas.edu.au