缺血再灌注后关节软骨中金属基质蛋白酶-3/组织抑制剂-1比例变化与关节软骨损伤的关系

Relation between the change in the ratio of matrix metalloproteinase-3 to tissue inhibitor of matrix metalloproteinase-1 and articular cartilage in rat after ischemia-reperfusion injury

目的探讨缺血再灌注后关节软骨中金属基质蛋白酶-3/组织抑制剂-1(MMP-3/TIMP-1)比例变化与软骨破坏、关节功能障碍的因素。方法采用大鼠后肢股动脉夹闭的方法模拟缺血再灌注的动物模型,用Wistar大鼠40只,随机分成正常对照组(NG)、肢体单纯缺血组(IG)和缺血再灌注组(IR)。运用免疫组化技术,分别测定TIMP-1和MMP-3在关节软骨中不同时相的表达变化并进行半定量分析,观察关节软骨病理改变及蛋白多糖(PG)的变化。结果缺血再灌注后,关节软骨中的MMP-3和TIMP-1表达均有增加,但MMP-3增加的幅度大于TIMP,导致MMP-3/TIMP-1比值增大,与再灌注后引起的关节软骨损伤相关。结论MMP/TIMP的失平衡表达是导致缺血再灌注后关节软骨损伤的重要因素。

AIM:To investigatethe relationship between the ratio of matrix metalloproteinase 3(MMP 3)to tissue inhibitor of MMP (TIMP 1) and articular cartilage injury after ischemia reperfusion.METHODS: Rats' hind limber femoral arteries were clapped to establish an animal ischemia reperfusion model.Forty Wistar rats were divided into three groups: normal control group (NG), ischemia group(IG), ischemia reperfusion group(IR). The expressions of TIMP 1 and MMP 3 were estimated with immunohistochemistry and analyzed semiquantively at different time points after ischemia reperfusion. The cartilage pathologic progresses and changes of proteoglycans (PG) were observed. RESULTS: After ischemia reperfusion, the expressions of MMP 3 and TIMP 1 both increased, but the expression of MMP 3 increased more quickly than that of TIMP. Ratios of MMP 3 to TIMP 1 increased, showing an imbalanced expression related with articular cartilage injury. CONCLUSION: The imbalance expression of MMP 3/TIMP is an important factor resulting in articular cartilage injury after ischemia reperfusion injury.