Molecular weight-dependent effects of hyaluronate on the arthritic synovium
Molecular weight-dependent effects of hyaluronate on the arthritic synovium
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DOI：
10.1679/aohc.61.125
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发表时间：
1998-05-01
影响因子：
--
通讯作者：
Uchiyama, K
中科院分区：
文献类型：
--
作者：
Asari, A;Miyauchi, S;Uchiyama, K
关节内注射透明质酸（HA）广泛用于治疗关节病。然而，HA制剂对关节炎滑膜的作用机制及其作用与分子量（MW）之间的关系仍不清楚。本研究的目的只是比较两种透明质酸盐制剂HA84（MW：84X10（4））和HA230（MW：230X10（4））对关节炎模型滑膜的影响，并检查HA影响的机制。将HA制剂关节内注射到前交叉韧带横断诱发的犬关节炎模型中，总共试验5周。为了确定 HA 制剂对滑膜内层的可及性，在最后一次给药时注射了荧光素标记的 HA84 或 HA230。分析的病理变化包括滑液中体积和前列腺素 E-2 浓度的增加、滑膜衬层增厚、衬层细胞中的空泡改变以及滑膜中 HA 的染色性。通过免疫组织化学方法检测组织中热休克蛋白 72 (Hsp72) 的表达水平，以研究细胞在变性中存活的能力。上述病理变化在HA230治疗组中仅仅比在HA230治疗组中得到更显着的抑制。在HA84治疗组的大多数病例中（六例中的五例），荧光素颗粒强烈分布在滑膜衬里层中，但HA230治疗组中只有两例显示荧光素颗粒在层中的弱分布，表明两种HA分子之间HA制剂对衬里细胞的可及性存在一定差异。此外，HA84处理组的衬里细胞中Hsp72的免疫反应性比HA230处理组更强烈。 HA 分子可及性的差异与衬里细胞中 Hsp72 的诱导能力的差异很好地对应。这些结果表明Hsp72的上调可能为HA制剂对关节炎滑膜的作用机制提供新的概念。
Intra-articular injection of hyaluronate (HA) is widely used in the treatment of arthropathies. However, the mechanism of the effects of HA preparations on the arthritic synovium and the relationship between their effects and molecular weights (MW) remains unknown. The objectives of this study mere to compare the effects of two hyaluronate preparations, HA84 (MW: 84X10(4)) and HA230 (MW: 230X10(4)), on the synovium of an arthritis model and to examine the mechanism of the effects of HA. The HA preparations were intra-articularly injected in a model of canine arthritis induced by anterior cruciate ligament transection for a total trial of 5 weeks. To define the accessibility of HA preparations to the synovial lining layers, fluorescein-labeled HA84 or HA230 was injected at the last administration. Pathological changes analyzed included increases in volumes and prostaglandin E-2 concentrations in synovial fluids, thickening of the synovial lining layers, vacuolar alterations in the lining cells, and stainability of HA in the synovium. Expression levels of Heat shock protein 72 (Hsp72) were immunohistochemically detected in the tissues to investigate the ability of the cells to survive the degeneration. The pathological changes described above mere more significantly suppressed in the HA230-treated than in the HA230-treated groups. In most cases of the HA84-treated group (five cases out of six), fluorescein particles were intensely distributed in the synovial lining layers, but only two cases in the HA230-treated group showed a weak distribution of fluorescein particles in the layers, indicating a certain difference in the accessibility of HA preparations to the lining cells between the two HA molecules. Moreover, the immunoreactivity for Hsp72 in the lining cells as more intense in the HA84-treated than in the HA230-treated groups. The difference in the accessibility of HA molecules corresponded well with that in the inducibility of Hsp72 in the lining cells. These results suggest that the up-regulation of Hsp72 may offer a new concept concerning mechanism of the effects of HA preparations on the arthritic synovium.