膝关节软骨早期缺损修复中的基质金属蛋白酶3抑制剂Ⅰ  

Matrix metalloproteinase-3 inhibitor I accelerates the early-stage repair of full-thickness articular cartilage defects in the knee of rats

作　　者：董福[1] 宋锦旗 姜楠 陆春[1] 

机构地区：[1]北海市人民医院骨科一区,广西壮族自治区北海市536000 [2]深圳市龙华新区中心医院创伤骨科,广东省深圳市518110 [3]广东省骨与软骨再生医学重点实验室,广东省广州市510515

出　　处：《中国组织工程研究》2016年第15期2156-2162,共7页Chinese Journal of Tissue Engineering Research

基　　金：北海市科学研究与技术开发计划项目(201405003);深圳市卫生计生系统博士创新项目资助课题(201505028)~~

摘　　要：背景:关节软骨损伤后,自然状态下修复的新生组织属于纤维软骨组织,其机械性能与正常软骨组织相差甚远,不能满足关节功能的需求,在后期逐渐退化,出现创伤性关节炎,最终导致关节功能破坏。目的:评价不同水平基质金属蛋白酶3抑制剂Ⅰ对大鼠膝关节软骨早期缺损促进修复的作用。方法:24只SD大鼠随机选取6只作为空白对照组,另18只大鼠制备膝关节软骨缺损模型后随机分为缺损组、缺损+低浓度抑制剂组及缺损+高浓度抑制剂组,后2组大鼠每周分别进行膝关节腔内注射不同浓度基质金属蛋白酶3抑制剂Ⅰ,共注射4周,6周结束实验。于实验前、实验后分别ELISA法测定血清基质金属蛋白酶3,并计算实验后、前的差值。实验后切开关节行大体观察评分,软骨缺损处组织予蕃红O-固绿染色行组织学观察、O’Driscoll组织评分,免疫组织化学检测软骨Ⅱ型胶原表达。结果与结论:(1)组织学切片显示:缺损组软骨缺损处纤维组织填充,缺损+低浓度抑制剂组乳白色的类软骨组织填充,缺损+高浓度抑制剂组半透明的类软骨组织填充,与周围正常软骨紧密结合;大体评分、O’Driscoll组织评分与Ⅱ型胶原表达:对照组>缺损+高浓度抑制剂组>缺损+低浓度抑制剂组>缺损组(P<0.05)。(2)基质金属蛋白酶3质量浓度:实验后,各组基质金属蛋白酶3质量浓度均升高,缺损组>缺损+低浓度抑制剂组>缺损+高浓度抑制剂组>对照组(P<0.05)。(3)基质金属蛋白酶3质量浓度差值:缺损组>缺损+低浓度抑制剂组>缺损+高浓度抑制剂组>对照组(P<0.05)。结果提示膝关节腔内注射基质金属蛋白酶3抑制剂Ⅰ可抑制基质金属蛋白酶3的过度表达,对大鼠膝关节软骨早期缺损的修复有一定的促进作用。BACKGROUND： The biomechanical properties of naturally regenerated damaged articular cartilage that belongs to the fibrovascular tissue are far worse than those of the normal cartilage so that they cannot meet the requirements for joint function, leading to traumatic arthritis and loss of joint function. OBJECTIVE： To evaluate the effects of matrix metalloproteinase-3（MMP-3） inhibitor I with different concentrations on the early-stage repair of full-thickness articular cartilage defects in the knee of rats. METHODS： Twenty-four Sprague Dawley rats were randomized into control, defect（DEF）, and defect combined with low-（D＋L） and high-dose inhibitor（D＋H） groups（n=6 for each group）, respectively. Full-thickness articular cartilage defects followed by intraarticular injection of low- and high-dose MMP-3 inhibitor I for 4 weeks was administered in the later two groups. Serum MMP-3 was detected using ELISA method before and after experiment, respectively. Femoral trochleas were collected to observe characteristics of repaired tissue by gross appearance scoring and O＇Driscoll histological scoring with Safranine O-Fast Green staining, and to measure type II collagen by immunohistochemistry after experiment. RESULTS AND CONCLUSION： Rats in the D＋H group had obvious repair similarly to hyaline articular cartilage, while creamy white cartilage tissue and fibrous tissue repair were observed in D＋L group and in DEF group. D＋H group obtained the best repair results according to gross appearance scoring and O＇Driscoll histological scoring and the highest content of type II collagen（P〈0.05）. MMP-3 concentration and the difference value before and after experiment were gradually decreased in DEF, D＋L, D＋H, and control groups in sequence（P〈0.05）. These findings demonstrate that MMP-3 inhibitor I accelerates the early-stage repair of full-thickness articular cartilage defects in the knee of rats.

关 键 词：基质金属蛋白酶3 软骨 关节 组织工程 组织构建 软骨组织工程 基质金属蛋白酶3抑制剂Ⅰ 关节软骨缺损 早期修复 基质金属蛋白酶3 组织学观察 免疫组织化学 Ⅱ型胶原 

分 类 号：R318[医药卫生—生物医学工程]