Inorganic pyrophosphate pool size and turnover rate in arthritic joints.
Inorganic pyrophosphate pool size and turnover rate in arthritic joints.
复制标题
关节炎关节中无机焦磷酸池的大小和周转率。
DOI：
10.1172/jci108056
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发表时间：
1975
期刊：
影响因子：
--
通讯作者：
C. SiLcox
中科院分区：
文献类型：
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作者：
Monique Camerlain;Daniel;J.;McCarty;Donald;C. SiLcox
最近的研究表明，相对于正常或关节炎受试者的静脉血浆中发现的PPi水平，来自假性痛风（PG）或骨关节炎（OA）患者的大多数膝关节液上清液中的无机焦磷酸盐（PPi）水平升高，并且来自痛风或类风湿性关节炎（RA）患者的一些上清液中的水平更适度升高。我们测量了关节内PPi池及其周转率，以更好地了解关节液-血浆PPi梯度的意义。对家兔的初步研究表明，（32-P）PPi从关节间隙进入血液，反之亦然，没有可检测到的水解。孵育的天然或合成的焦磷酸钙二水合物（CPPD）的微晶与滑液在体外（32 P）PPi示踪剂的存在下，在上清液中的PPi比活性在19小时内没有变化，使PPi在溶液中的交换与CPPD微晶可以忽略不计。（32 P）PPi和（33 P）Pi的清除率，通过连续采样不同类型关节炎的志愿者的膝关节导管在3小时内，几乎是相同的。测定各样品中的（32 P）PPi/（32 P）Pi。大量过量的冷PPi的混合物不影响任一核素的清除率。根据同位素稀释和周转率确定的样本池大小计算每小时周转的PPi数量。残留关节液核素为（32 P）PPi。PPi池通常较小，临床炎症关节的周转率较高。平均正负SEM样本池大小（μ-摩尔）和周转率PG膝关节为0.23 ± 0.07和117 ± 11.9，水解率（%/h）为27.7 ± 13.2，OA膝关节为0.45 ± 0.26和72 ± 9.2，水解率为6.9 ± 0.9;在痛风膝盖：0.8 ± 0.41和50 ± 11.6，水解9.8 ± 2.8; RA膝关节：0.14 ± 0.14和114 ± 35.8，水解236 ± 116。PPi转换率（mumoles/小时）与关节中存在的OA变化程度相关，按照放射学标准分级，与临床诊断无关。晚期OA关节的平均PPi周转率高于轻度或中度变化的关节（P <0.001），但轻度和中度组无显著差异。我们的结论是，滑膜PPi营业额和PPi液浓度升高是不特定的PG患者，这些因素不能单独的CPPD晶体沉积的唯一决定因素。
Recent studies have shown elevated inorganic pyrophosphate (PPi) levels in most knee joint fluid supernates from patients with pseudogout (PG) or osteoarthritis (OA) and more modestly elevated levels in some supernates from patients with gout or rheumatoid arthritis (RA) relative to PPi levels found in the venous blood plasma of normal or arthritic subjects. We measured the intraarticular PPi pool and its rate of turnover to better understand the significance of the joint fluid-plasma PPi gradient. Preliminary studies in rabbits showed that (32-P)PPi passed from joint space to blood and vice versa without detectable hydrolysis. Incubation of natural or synthetic calcium pyrophosphate dihydrate (CPPD) microcrystals with synovial fluid in vitro in the presence of (32P)PPi tracer showed no change in PPi specific activity in the supernate over a 19-h period so that exchange of PPi in solution with that in CPPD microcrystals could be ignored. Clearance rates of (32P)PPi and of (33P)Pi, as determined by serially sampling the catheterized knee joints of volunteers with various types of arthritis over a 3-h period, were nearly identical. The (32P)PPi/(32P)Pi was determined in each sample. A mixture of a large excess of cold PPi did not influence the clearance rate of either nuclide. The quantity of PPi turned over per hous was calculated from the pool size as determined by isotope dilution and the turnover rate. The residual joint fluid nuclide was shown to be (32P)PPi. The PPi pool was generally smaller and the rate of turnover was greater in clinically inflamed joints. The mean plus or minus SEM pool size (mu-moles) and turnover rate (percent/hour) in PG knees was 0.23 plus or minus 0.07 and 117 plus or minus 11.9, hydrolysis rate (%/h) to Pi was 27.7 plus or minus 13.2; in OA knees: 0.45 plus or minus 0.26 and 72 plus or minus 9.2, hydrolysis 6.9 plus or minus 0.9; in gouty knees: 0.8 plus or minus 0.41 and 50 plus or minus 11.6, hydrolysis 9.8 plus or minus 2.8; and in RA knees: 0.14 plus or minus 0.14 and 114 plus or minus 35.8, hydrolysis 236 plus or minus 116. PPi turnover (mumoles/hour) correlated with the degree of OA change present in the joint as graded by radiologic criteria irrespective of the clinical diagnosis. Mean PPi turnover in joints with advanced OA was greater than in those with mild or moderate changes (P smaller than 0.001), but the mild and moderate groups showed no significant difference. We conclude that synovial PPi turnover and elevated PPi fluid concentrations are not specific for PG patients, and that these factors alone cannot be the only determinants of CPPD crystal deposition.