二膦酸盐对兔膝关节不稳早期软骨 下骨生化改变的影响

 目的观察兔膝关节不稳早期软骨下骨基质金属蛋白酶-9(matrix metallo proteinase-9,MMP-9)和组织蛋白酶K(cathepsinK,CK)的表达变化及二膦酸盐的抑制作用,探讨其机制及二膦酸盐的作用途径。方法健康雄性新西兰大白兔50只,随机数字表法分为对照组(n=10)、模型组(n=20)和二膦酸盐组(n=20)。采用Hulth兔膝关节不稳模型的制作方法右侧膝关节造模,分别于造模后2周和10周行空气栓塞处死,各时相点模型组和二膦酸盐组各取10个右膝关节的股骨内侧髁,对照组取5个右膝关节的股骨内侧髁,用SP免疫组织化学染色方法检测各组在2周和10周时软骨下骨MMP-9和CK的表达变化,并进行比较分析。结果对照组、二膦酸盐组和模型组在兔膝关节不稳造模后2周时均有MMP-9和CK阳性表达细胞,MMP-9阳性表达率分别为4%、10%和92%,CK阳性表达率分别为8%、12%和90%;10周时亦均有MMP-9和CK阳性表达细胞,MMP-9阳性表达率分别为4%、8%和72%,CK阳性表达率分别为8%、10%和68%。二膦酸盐能明显减少MMP-9和CK阳性表达;与模型组比较差异有统计学意义。 结论二膦酸盐可阻抑兔膝关节不稳早期软骨下骨MMP-9和CK的表达,抗骨吸收以减少软骨下骨的病理改变,从而保护关节软骨。

Effect of diphosphonate on biochemistry change in subchondral bone of unstable rabbit knee joints

Objective To explore the effect of diphosphonate on expression of matrix metalloproteinase-9(MMP-9) and cathepsin K(CK) in subchondral bone of unstable rabbit knee joints. Methods Fifty male New Zealand white rabbits were divided randomly into three groups according to random digits table: the control group (n=10), the model group (n=20). the diphosphonate group (n=20). Hulth model of unstable rabbit knee joint was achieved in the right knee joint. Ten rabbits from the diphosphonate group and 5 rabbits from the control group were sacrificed by aeroembolism at the second and tenth week postoperatively, respectively. Then the medial femoral condyles of the right knee were harvested. Specimens were processed for immunohistochemical analysis of MMP-9 and CK. Results Cells with expression of MMP-9 and CK could be found in the three groups at the second and tenth week after operation. Compared with the control group, there was a significant increase in the number of cells with expression of MMP-9 and CK in model group at the second and tenth week after operation. Diphosphonate could inhibit expression of MMP-9 and CK in cells. Compared with the model group, the number of cells with expression of MMP-9 and CK in diphosphonate group was fewer; there was a statistical significance between them. Conclusion Diphosphonate can inhibit the expression of MMP-9 and CK in subchondral bone of unstable rabbit knee joints, which can resist the bone resorption and protect articular cartilage.