膝骨性关节炎患者滑膜水通道蛋白-1表达与血管生成的相关性研究

Studies on correlation between angiogenesis and the synovial aquaporins- 1 expression in patients with knee osteo-arthritis

[目的]观察膝骨性关节炎(knee osteoarthritis,KOA)患者滑膜中水通道蛋白1(aquaporins-1,AQP-1)表达和血管生成的情况,并对二者进行相关性分析,从而探讨AQP-1表达与血管生成在KOA滑膜炎中的意义,为进一步研究膝骨性关节炎(osteoarthritis,OA)的发病机制提供试验依据。[方法]根据Kellgren-Lawrence(K/L)分级和美国风湿病协会KOA标准,将50例患者分为早期KOA组、晚期KOA组和正常组。对获取的膝关节样本行术中肉眼观察和显微镜下组织学观察,并用Krenn滑膜炎评分评估滑膜组织学变化。采用免疫组化法检测滑膜组织中AQP-1和CD34的表达情况。显微镜下观察CD34单克隆抗体标记新生血管内皮细胞微血管计数,并进行微血管密度(MVD)的计算。采用Pearson线性相关性分析法分别对MVD与滑膜炎性评分之间,AQP-1阳性细胞表达率与滑膜炎评分之间,AQP-1阳性细胞表达率与MVD之间进行相关性分析。[结果](1)在早期KOA组和晚期KOA组膝关节滑膜中都有滑膜炎性改变,其主要变化为:滑膜衬里层增生、血管增生和炎性细胞浸润。KOA组滑膜炎性评分较正常组明显高,差异具有统计学意义(P<0.05),且早期KOA组滑膜较其他两组滑膜炎性等级更高,差异具有统计学意义(P<0.05);(2)免疫组化检测结果显示,与正常滑膜组织相比,在KOA组滑膜中AQP-1和MVD有着更高的表达,差异具有统计学意义(P<0.05),且早期KOA组高于晚期KOA组,差异具有统计学意义(P<0.05);(3)MVD值与滑膜炎性评分呈明显正相关(r=0.825,P<0.01);AQP-1阳性细胞表达率与滑膜炎性评分呈明显正相关(r=0.827,P<0.01);AQP-1阳性细胞表达率与MVD值明显正相关(r=0.894,P<0.01)。[结论](1)AQP-1的表达和新生血管生成在KOA组较正常组明显增多,早期KOA组较晚期KOA组明显增多,且AQP-1表达的上调可能与滑膜血管生成相关;(2)KOA滑膜中AQP-1表达上调和血管生成可能通过协调作用参与了人KOA滑膜炎的形成及KOA的发生、发展。

To explore the effect of the AQP - 1 expression and angiogenesis on the KOA synovitis and to pro- vide the experimental basis for further study of knee osteoarthritis by observing angiogenesis and the synovial aquaporins - 1 ex- pression in patients with knee osteoarthritis and analyzing their correlations. [ Methods] According to the Kellgren - Lawrence （K/L） classification and the American Rheumatism Association KOA standards, 50 patients were divided into three groups： early KOA group, late KOA group and normal group. Then macroscopic observation of knee joint sample line and histological ob-servation under a microscope were carried out, and synovial histological changes were evaluated by Krenn synovitis score. The AQP1 and CD34 expression in the synovial tissue were decided through the immunohistochemical detection. New endothelial ceils marked by Microscope CD34 monoclonal antibody were counted, and the microvascular density （MVD） was calculated. With Pear- son linear correlation analysis, the correlations between MVD, synovitis score, and the expression rate of AQP - 1 positive cellswere analyzed respectively. [ Results ] （ 1 ） Knee joint synovials in the early KOA group and late KOA group showed inflamma- tory changes. The main changes were synovial lining layer hyperplasia, vascular proliferation and inflammatory cell invasion. The synovial inflammation of KOA group scores was markedly higher than that of the normal group, with significant difference （P 〈 0.05 ）, and the synovial inflammation of the early KOA group levels higher than other two groups, with rather sharp difference （P 〈 0.05 ） ; （2） The immunohistochemical detection results showed that compared with the normal synovial tissue, AQP - 1 and MVD of the KOA group had a higher expression （P 〈 0. 05）, and compared with the late KOA group, AQP - 1 and MVD of the early KOA group had a higher expression （ P 〈 0. 05 ） ; （ 3 ） The MVD value showed markedly positive correlation with the synovial inflammation score （ r = 0. 825, P 〈 0.01 ） ; the AQP - 1 positive expression rate indicated significantly positive correlation with the synovial cell inflammatory score （ r = 0. 827, P 〈 0. 01 ） ; the AQP - 1 positive cell expression rate had obvi- ously positive correlation with the MVD value （ r = 0. 894, P 〈 0.01 ） . [ Conclusion] （ 1 ） AQP - 1 expression and new an- giogenesis of the KOA group increase significantly compared with those of the normal group, and those of the early KOA group grow relatively compared with those of the late KOA group ; and the higher AQP - 1 expression may be associated with synovial angiogenesis; （2） Through coordinating the higher AQP - 1 expression in the KOA synovium and angiogenesis may have the effect on the formation of the patients KOA synovitis and the occurrence and development of KOA.