血管内皮细胞生长因子在骨关节炎患者膝关节滑膜和滑液中的表达及其意义

目的 检测不同阶段的骨关节炎患者膝关节滑膜组织和滑液中血管内皮细胞生长因子(VEGF)的表达情况，评价VEGF作为进展期骨关节炎的标志的可行性。方法 临床收集膝关节镜或关节置换手术患者的滑液和滑膜组织，根据X线平片的K-L分级进行分组。以Kellegren-Lawrence (K-L)分级均为0级的单纯膝关节半月板损伤的患者作为对照组。酶联免疫吸附测定( ELISA)法检测各组滑液中VEGF的含量，免疫组织化学染色方法检测VEGF在滑膜组织中的原位表达。统计学方法采用方差分析。结果 骨关节炎滑膜组织普遍存在不同程度的炎症，滑膜色泽变暗红，组织增生，甚至呈绒毛样改变。免疫组织化学染色显示，VEGF在滑膜衬里层及血管平滑肌细胞表达。2～4组的滑液中VEGF水平逐级增高，从(1181±116)、(1632±140)到(2252±216) pg/ml，明显高于对照组(648±129) pg/ml，差异均有统计学意义（P＜0.01）；免疫组织化学阳性细胞分数对照组和第2～4组分别为(5±4)％和(9±4)％、(16±6)％、(21±6)％，差异有统计学意义(P＜0.01)。结论 关节滑膜产生的VEGF参与了骨关节炎软骨损害的病理过程，滑液中VEGF水平的持续升高可作为判断骨关节炎病情活动的一个指标。

The expression and significance of vascular endothelial growth factor in knee synovial membranes and synovial fluids of patients with osteoarthritis

Objective To investigate the expression levels of vascular endothelial growth factor (VEGF)in knee synovial membranes and synovial fluids whether it could be a marker for progressive osteoarthritis.Methods Knee synovial membranes and synovial fluids of patients with osteoarthritis who were underwent total knee arthroplaaty or arthroscopy were collected. They were classified into four groups according to the radiographic gradingKellegren-Lawrence (K-L) grade]. Appoint K-L-0-grade patients who suffered from menisci injuries only served as controls. The levels of VEGF in the synovial fluid were measured by enzymelinked immunosorbent assay (ELISA) and VEGF-secreting cells were identified by immunohistochemistry.ANOVA was used for statistical analysis. Results Various degrees of inflammation could be found in all the samples evaluated histologically on HE-stained sections. Synovial tissue inflammation presented as synovial lining thickening, and inflammatory cells infiltration. VEGF expressed in the synovium linings and surrounding blood vessels. The VEGF levels in the synovial fluids were increased accordingly with K-L grades, which reached the peak level in the late stage of osteoarthritis. The levels of VEGF in the synovial fluids were significantly higher in patients with osteoarthritisfrom (1181±116), (1632±140) to (2252±216) pg/ml]than in those with menisci injury (P＜0.01); The percent ages positive cell in each groups were (5±4)％ , (9±4)％,(16±6)％ and (21±6)％ respectively, there were significantly differences too (P＜0.01). Conclusion VEGF originated from synovial tissue may play a role in the pathogenesis of osteoarthritis. High levels of VEGF in the synovial fluids can be regarded as the marker of active osteoarthritis.