诱导型一氧化氮合酶和白介素1受体拮抗剂在骨关节炎滑膜和软骨中的表达及意义

炎症前细胞因子白介素 1(IL - 1)通过刺激软骨细胞合成诱导型一氧化氮合酶 (iNOS) ,产生一氧化氮(NO) ,增加基质降解 ,参与关节炎的炎症活动 ,而局部产生的白介素 1受体拮抗剂蛋白 (IL - 1Ra)可阻止软骨破坏。本实验旨在观察iNOS和IL - 1Ra在骨关节炎 (OA)关节滑膜和软骨中的表达及分布。我们收集了 6例OA患者的关节滑膜和软骨标本。通过免疫组化方法对iNOS、CD6 8和IL - 1Ra进行了原位检测。在 6例OA滑膜标本连续切片中 ,滑膜的衬里层细胞、炎症浸润细胞以及血管内皮细胞中均强烈表达iNOS蛋白。IL - 1Ra阳性细胞主要局限于滑膜的衬里层细胞及血管内皮细胞 ,表达强度低于iNOS表达。CD6 8阳性细胞 (检测巨噬细胞的抗体 )仅在滑膜衬里层的表层 (A型滑膜细胞 )及炎症浸润细胞中零星表达。在 6例骨关节炎软骨连续切片标本中 ,iNOS和IL - 1Ra在软骨全层及软骨下骨髓腔内均有强烈表达。结果提示 ,骨关节炎时 ,iNOS主要产生于滑膜衬里层细胞、软骨细胞以及血管内皮细胞 ,而IL - 1Ra主要产生于滑膜衬里层的巨噬样滑膜细胞和软骨细胞 ;iNOS和IL - 1Ra之间的拮抗作用可能在骨关节炎的病理机制中发挥很重要的作用。

Induced Nitric Oxide Synthase and Interleukin 1 Receptor Antagonist Protein Production and Effect in Synovial and Chondral Tissue from Patients with Osteoarthritis

Interleukin 1(IL-1)is a proinflammatory factor and can participate in the perpetuation of arthritis through stimulating the synthesis of induced nitric oxide synthase(iNOS)by chondrocytes and synoviocytes,and augmentation of matrix degradation.Hence ,local production of the IL-1 receptor antagonist protein(IL-1Ra)might be an important negative feedback signal that regulates cartilage damage.This experiment is aimed at investigating the expression and localization of iNOS and IL-1Ra in human arthritis- affected sy noviocytes and chondrocytes.We assessed iNOS and IL-1Ra production respectively in synovium and cartilage from 6 osteoarthritis(OA) individuals,by using histology and immunohistochemistry staining method.In synovial consecutive slice samples of 6 cases from OA,iNOS was predominantly expressed in synovial lining cells ,inflammatory infiltrating cells,endothelial cells.IL-1Ra was expressed in synovial lining cells and endothelial cells,and less than iNOS in expressive level.The synovial lining cells expressing IL-1Ra were identified where CD68 cells were located,together with morphological features,this suggests that they are type A sy- noviocytes. In chondral consecutive slice samples of 6 cases from OA,intense expression of both iNOS and IL-1Ra were observed in whole cartilage and marrow cavity under cartilage.In OA,iNOS is produced primarily by synovial lining cells,chondrocytes and endothelial cells,and IL-1Ra is produced mainly by CD68 synoviocytes and chondrocytes.The contrary effect between iNOS and IL-1Ra may play a key role in the pathogenesis of OA.