p38阻断剂对鼠关节炎软骨细胞金属蛋白酶表达的作用  

Effects of Intra-articular Injection of p38 Mitogen-activated Protein Kinase Inhibitor on Matrix Metalloproteinase in Articular Cartilage of a Rat Model of Osteoarthritis

作　　者：陈蔚东[1] 蒋青[1] 陈东阳[1] 徐华[1] 张亚峰[1] 

机构地区：[1]南京大学医学院附属鼓楼医院关节疾病诊治中心,南京210008

出　　处：《中国医学科学院学报》2007年第6期777-781,I0006,共6页Acta Academiae Medicinae Sinicae

基　　金：国家自然科学基金(30571874)~~

摘　　要：目的观察p38信号转导途径阻断剂SB203580经关节腔注射对实验性鼠膝骨关节炎基质金属蛋白酶(MMP)-3、MMP-13表达的影响,探讨MMP-3、MMP-13表达与创伤性软骨退变之间的关系。方法40只SD大鼠随机分为A～D组,每组10只。各组均行单侧膝关节前交叉韧带切除术。A、B组分别于术后立即行关节腔内注射0.1ml高、低浓度的p38阻断剂SB203580(100、10μmol/L),每周1次,连续6周。C组注射等量生理盐水,D组不做任何处理。术后7周处死动物。于解剖显微镜下行股骨关节面软骨退变大体观察,免疫组织化学的方法检测MMP-3、MMP-13在软骨中的表达及分布,Westernblot方法检测软骨中MMP-3、MMP-13蛋白表达水平。结果大体观察显示高、低浓度组软骨退变显著轻于生理盐水组和关节炎组(P<0.05);免疫组织化学显示高、低浓度组软骨MMP-3、MMP-13表达降低(P<0.05);Westernblot显示注射抑制剂后MMP-3、MMP-13的蛋白表达降低(P<0.01)。结论p38阻断剂SB203580能抑制MMP-3、MMP-13的表达,对软骨有一定的保护作用。Objective To observe the effect of intra-articular injection of SB203580, a selective p38 mitogen-activated protein kinase inhibitor, on the expression of matrix metalloproteinase （MMP）-3, MMP-13 in a rat model of osteoarthritis （OA） and to explore the relationship between the MMP-3/MMP-13 expressions （ACLT） and then randomly divided into four groups, with 10 rats in each group. Group A received 0. 1 ml intra-articular injection of SB203580 at a high concentration of 100μmol/L （ once a week） immediately after surgery, and group B were treated under the same condition using SB203580 with a low concentration of 10μmol/ L. Group C received 0. 1 ml intra-articular normal saline, and group D were not injected as controls after ACLT. All rats were sacrificed seven weeks after the surgery. Macroscopic and immunohistochemical studies Protein expressions of MMP-3 and MMP-13 were determined by Western blot. Results Cartilage degradation was significantly milder in group A and group B than in the control groups,as shown by morphological studies （P 〈 0. 05 ） and immunohistochemical studies （ P 〈 0. 05 ）. The protein expressions of MMP-3 and MMP-13 in cartilage were significantly lower in groups A and B than in groups C and D （P 〈0.01 ）. Conclusion SB203580 can inhibit the expressions of MMP-3 and MMP-13 and thus protect the cartilage.

关 键 词：骨关节炎 基质金属蛋白酶 信号转导 阻断剂 

分 类 号：R684.3[医药卫生—骨科学]