Lundberg C, Asberg I, Ionescu M, Reiner A, Smedegård G, Poole A R
Department of Pharmacology, Pharmacia Pharmaceutials Uppsala, Sweden.
Ann Rheum Dis. 1996 Aug;55(8):525-34. doi: 10.1136/ard.55.8.525.
To determine how acute but transient inflammation affects the cartilage proteoglycan aggrecan and the value of analyses of synovial fluid to study this.
For 96 hours after a single intra-articular injection of rabbit knees with human interleukin-1 alpha (IL-1 alpha) or vehicle, articular cartilage and synovial fluid were examined using a putative indicator of aggrecan synthesis (aggrecan chondroitin sulphate epitope 846), immunoreactive keratan sulphate, and total glycosaminoglycan (GAG) content. Aggrecan extractability (with 0.5 M NaCl) followed by 4 M guanidine hydrochloride extraction permitted analyses of cartilage damage, total content and aggrecan heterogeneity. Aggrecan epitopes as well as GAG were assayed in synovial fluid. Changes were related to total joint leucocyte content in synovial fluid.
At 10 ng, IL-1 alpha produced a transient increase in synovial fluid leucocytes at six hours and 24 hours. This accompanied a reduction in content and increased extractability of GAG, which was greatest in the tibial medial compartment of the knee. Further studies of this compartment showed no change in keratan sulphate epitope content, but a transient increase in extractability in 0.5 M NaCl. Epitope 846 content and extractability were unchanged. Total contents and extractability for GAG were inversely correlated in both controls and joints injected with IL-1 alpha. These changes were accompanied by transient increases in GAG, keratan sulphate epitope, and 846 content in synovial fluid.
According to the aggrecan component measured, damage to the matrix of articular cartilage was sometimes reflected by a transient increased extractability and a net loss of aggrecan. There was always an increased release of GAG, and keratan sulphate, and 846 epitopes into synovial fluid. These studies show that changes in aggrecan epitopes and GAG in synovial fluid reflect changes in cartilage metabolism induced by acute transient inflammation.
确定急性但短暂的炎症如何影响软骨蛋白聚糖聚集蛋白聚糖，以及分析滑液在研究这一过程中的价值。
在兔膝关节单次关节内注射人白细胞介素-1α（IL-1α）或赋形剂后96小时，使用聚集蛋白聚糖合成的假定指标（聚集蛋白聚糖硫酸软骨素表位846）、免疫反应性硫酸角质素和总糖胺聚糖（GAG）含量来检查关节软骨和滑液。聚集蛋白聚糖的可提取性（用0.5M氯化钠），随后用4M盐酸胍提取，用于分析软骨损伤、总含量和聚集蛋白聚糖的异质性。在滑液中检测聚集蛋白聚糖表位以及GAG。变化与滑液中全关节白细胞含量相关。
注射10ng IL-1α后，滑液白细胞在6小时和24小时出现短暂增加。这伴随着GAG含量的减少和可提取性的增加，在膝关节内侧胫骨间室最为明显。对该间室的进一步研究表明硫酸角质素表位含量没有变化，但在0.5M氯化钠中的可提取性短暂增加。表位846的含量和可提取性没有变化。在对照组和注射IL-1α的关节中，GAG的总含量和可提取性呈负相关。这些变化伴随着滑液中GAG、硫酸角质素表位和846含量的短暂增加。
根据所测量的聚集蛋白聚糖成分，关节软骨基质的损伤有时表现为聚集蛋白聚糖可提取性的短暂增加和净损失。GAG、硫酸角质素和846表位向滑液中的释放总是增加的。这些研究表明，滑液中聚集蛋白聚糖表位和GAG的变化反映了急性短暂炎症诱导的软骨代谢变化。
