兔膝关节骨性关节炎半月板形态改变及基质金属蛋白酶-3和金属蛋白酶组织抑制剂-1表达

Rabbit meniscus morphology change and expressions of matrix metalloproteinase-3 and tissue inhibitor of matrix metalloproteinase-1 in osteoarthritis

目的探讨家兔膝关节骨性关节炎的半月板形态改变及其基质金属蛋白酶-3(matrix metalloproteinase-3,MMP-3)、金属蛋白酶组织抑制剂-1(tissue inhibitor of matrix metalloproteinase-1,TIMP-1)表达情况,及半月板与膝骨性关节炎间关系和相互作用。方法雌性中国家兔24只,48个膝关节,分为实验组12个膝、模型组12个膝和正常对照组24个膝,实验组采用钢针在关节软骨划痕方法制作骨性关节炎模型,模型组仅给予关节切开,对照组不做处理。术后2、4、6周处死动物,对半月板行组织病理学检查,观察半月板细胞及胶原纤维形态变化;采用免疫组织化学法检测半月板MMP-3及TIMP-1表达情况,采用电子显微镜观察半月板胶原超微结构。结果实验组兔膝关节可见明显骨性关节炎改变,大体及组织病理学结果显示半月板退变、胶原破坏、软骨细胞变性坏死;实验组第2、4、6周时,半月板MMP-3水平(118.16±2.11、127.35±1.87、141.02±2.54)和第4、6周时TIMP-1水平(136.76±1.62、157.03±1.25)明显高于模型组(MMP-3为92.43±1.57、95.38±2.89、99.74±2.17,TIMP-1为91.11±3.02、106.54±1.13)和对照组(MMP-3为92.15±1.68、96.63±2.07、101.41±1.75,TIMP-1为91.08±2.21、107.47±1.76)(P<0.05),模型组与对照组比较差异均无统计学意义(P>0.05)。结论膝骨性关节炎可造成半月板生物力学和生化环境紊乱,半月板组织结构退变、功能丧失可进一步加重骨性关节炎病变。

Objective To explore the pathological changes of meniscus in osteoarthritis knee and the expressions of matrix metalloproteinase-3（MMP-3）and tissue inhibitor of matrix metalloproteinase-1（TIMP-1）in osteoarthritis,and the relationship between meniscus and osteoarthritis.Methods Twenty-four female Chinese rabbits（48knees）were randomly divided into experimental group（12 knees）,model group（12 knees）and control group（24 knees）.Experimental group was established knee osteoarthritis models by making grooves on the cartilage surface,model group underwent arthrotomy,and control group received no treatment.The rabbits were sacrificed after 2,4and 6weeks after operation.The meniscus received histopathologic examination to observe the morphologic changes of cell and collagen fiber.Immunohistochemistry was used to detect the expressions of MMP-3 and TIMP-1,and scanning electron microscope was used to observe ultramicrostructure of meniscus collagen fibers.Results Experimental group presented obvious osteoarthritis,and histopathologic results showed meniscus degeneration,collage damage and cartilage cell necrosis.The expressions of MMP-3in 2,4and 6 weeks（118.16±2.11,127.35±1.87,141.02±2.54）,and the expressions of TIMP-1in 4and 6weeks（136.76±1.62,157.03±1.25）in experimental group were higher than those in model group（MMP-3：92.43±1.57,95.38±2.89,99.74±2.17;TIMP-1：91.11±3.02,106.54±1.13）and control group（MMP-3：92.15±1.68,96.63±2.07,101.41±1.75;TIMP-1：91.08±2.21,107.47±1.76）（p〈0.05）,and there were no significant differences between model group and control group（p〈0.05）.Conclusion Osteoarthritis causes the changes of biomechanical and biochemistry environment around meniscus.The degeneration and dysfunction of meniscus aggravate can osteoarthritis.