基质金属蛋白酶9及TGF-β_1 mRNA和蛋白在骨关节炎中的表达  

SIGNIFICANCE OF EXPRESSIONS OF MATRIX METALLOPROTEINASE 9 mRNA, TRANSFORMING GROWTH FACTOR β_1 mRNA AND CORRESPONDING PROTEINS IN OSTEOARTHRITIS

作　　者：郭静[1] 张文丽[1] 李琪佳[1] 甘洪全[2] 王志强[2] 

机构地区：[1]河北联合大学医学实验研究中心,河北唐山063000 [2]河北联合大学附属医院骨科

出　　处：《中国修复重建外科杂志》2011年第8期992-997,共6页Chinese Journal of Reparative and Reconstructive Surgery

基　　金：河北省人事厅留学归国人员科技活动基金资助项目(200911)~~

摘　　要：目的 TGF-β1对骨关节炎(osteoarthritis,OA)关节软骨起保护作用,探讨OA中基质金属蛋白酶9(matrix metalloproteinase 9,MMP-9)、TGF-β1 mRNA和蛋白表达的相关性,为临床治疗OA寻找有效的干预靶点提供理论依据。方法取自愿捐赠的关节软骨及滑膜标本,其中OA患者60例(实验组),外伤截肢、交叉韧带断裂、盘状软骨损伤与半月板损伤患者20例(正常对照组)。行HE染色观察关节软骨与滑膜的病理组织学改变,免疫组织化学染色观测MMP-9及TGF-β1蛋白表达,原位杂交技术检测MMP-9及TGF-β1 mRNA表达;并进行相关性分析。结果 HE染色显示实验组关节软骨细胞固缩、坏死、排列紊乱,细胞外基质断裂,关节滑膜细胞肥大增生、淋巴细胞和单核细胞浸润,多数小血管增生;正常对照组软骨细胞排列整齐、基质染色均匀,滑膜组织无慢性炎症表现、无明显增生。两组均可见MMP-9、TGF-β1 mRNA和蛋白阳性表达,阳性细胞包括软骨细胞、滑膜衬里层细胞及滑膜下层的血管内皮细胞、成纤维细胞、炎性浸润细胞等。实验组MMP-9及TGF-β1 mRNA和蛋白表达均高于正常对照组(P<0.01)。实验组MMP-9 mRNA与蛋白表达成正相关(r=0.924,P=0.000),TGF-β1 mRNA及蛋白表达亦成正相关(r=0.941,P=0.000);实验组MMP-9及TGF-β1蛋白表达成负相关(r=—0.762,P=0.000),MMP-9 mRNA及TGF-β1 mRNA表达成负相关(r=?0.681,P=0.000)。结论 OA中TGF-β1的高表达下调了关节软骨与滑膜中MMP-9的表达,对OA关节软骨起保护作用,从而延缓OA进展。Objective It is reported that transforming growth factor β1 （TGF-β1） has the protective effects on the articular cartilage in osteoarthritis （OA）. To investigate the significance of the expressions of matrix metalloproteinase 9 （MMP-9）, TGF-β1 mRNA and corresponding proteins in OA. Methods The specimens of articular cartilage and synovium were collected from voluntary donators, including 60 cases of OA （experimental group） and 20 cases of traumatic amputation, cruciate ligament rupture, discoid cartilage injury, and menisci injury （normal control group）. The pathological changes were observed by HE staining. MMP-9 and TGF-β1 protein expressions were detected by immunohistochemical technique, and the mRNA expressions of MMP-9 and TGF-β1 were detected through in situ hybridization technique; and their correlation was analysed. Results HE staining showed： shrinkage, necrosis, and irregular arrange of the articular chondrocytes, extracellular matrix fracture, hypertrophy and hyperplasia synovium, infiltration of lymphoid and mononuclear cells and proliferation of many small blood vessels in the experimental group; regular arrangement of the articular chondrocytes, the homogeneously staining matrix, and synovial tissue without chronic inflammation and significant proliferation in the normal control group. The mRNA and protein expressions of MMP-9 and TGF-β1 were positive in 2 groups. The positive-stained cells included chondrocytes, synovial lining cells, and vascular endothelial cells, fibroblasts, and inflammatory infiltrated cells in subsynovial layer. The expressions of mRNA and corresponding protein of MMP-9 and TGF-β1 in the experimental group were significantly higher than those in the normal control group （P 〈 0.01）. There was a positive correlation between MMP-9 mRNA and protein expression （r=0.924, P=0.000）, and between TGF-131 mRNA and protein expression （r=0.941, P=0.000） in the experimental group. There was a negative correlation between the expression of MMP-9 p

关 键 词：骨关节炎 基质金属蛋白酶9 TGF-β1 原位杂交 免疫组织化学染色 

分 类 号：R684.3[医药卫生—骨科学]