中国组织工程研究

中国组织工程研究 ›› 2016, Vol. 20 ›› Issue (15): 2156-2162.doi: 10.3969/j.issn.2095-4344.2016.15.004

• 软骨组织构建 cartilage tissue construction • 上一篇    下一篇

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

董 福1，宋锦旗2，姜 楠3，陆 春1   

  1. 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
  • 收稿日期:2016-01-30 出版日期:2016-04-08 发布日期:2016-04-08
  • 作者简介:董福，男，1981年生，广西壮族自治区北海市人，汉族，2013年南方医科大学骨外科专业毕业，硕士，主治医师，主要从事创伤骨科的研究。
  • 基金资助:

    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)

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

Dong Fu1, Song Jin-qi2, Jiang Nan3, Lu Chun1   

  1. 1Department of Orthopedics, Beihai People’s Hospital, Beihai 536000, Guangxi Zhuang Autonomous Region, China; 2Department of Orthopedics, Central Hospital of Longhua District, Shenzhen 518110, Guangdong Province, China; 3Key Laboratory of Bone and Cartilage Regenerative Medicine of Guangdong Province, Guangzhou 510515, Guangdong Province, China
  • Received:2016-01-30 Online:2016-04-08 Published:2016-04-08
  • About author:Dong Fu, Master, Attending physician, Department of Orthopedics, Beihai People’s Hospital, Beihai 536000, Guangxi Zhuang Autonomous Region, China
  • Supported by:

    the Scientific Research and Technology Development Program of Beihai City, China, No. 201405003; the Medical Doctoral Innovation Project Funding of Shenzhen Health Development Planning Commission, No. 201505028

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摘要：

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文题释义：
金属蛋白酶抑制剂：是基质金属蛋白酶的特异性抑制物，通过氨基末端决定簇与金属蛋白酶按1∶1结合而抑制其活性，对抗金属蛋白酶对基质及胶原蛋白的降解，促进软骨损伤的修复。正常状态下金属蛋白酶与抑制剂的分泌保持动态平衡，受到外界因素干扰后平衡被打破。
关节软骨：关节软骨属于透明软骨，表面光滑，呈淡蓝色，有光泽，它是由一种特殊的叫做致密结缔组织的胶原纤维构成的基本框架，这种框架呈半环形，其底端紧紧附着在下面的骨质上，上端朝向关节面，关节软骨紧密与骨结合不会掉下来，同时当受到压力的时候还可以有少许的变形，起到缓冲压力的作用。在这些纤维之间，散在分布着软骨细胞，软骨细胞由浅层向深层逐渐由扁平样至椭圆或圆形细胞组成，维持关节软骨的正常代谢。关节软骨没有神经血管支配，其营养成分必须从关节液中取得，其代谢废物也必须排至关节液中，这种营养代谢必须通过关节运动，使关节软骨不断的受到压力刺激才行，所以关节运动对于维持关节软骨的正常结构可起到重要的作用。
 

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。
中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程
ORCID: 0000-0002-0428-2485(董福)

关键词: 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

Abstract:

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.
中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

Key words: Matrix Metalloproteinase 3, Cartilage, Articular, Tissue Engineering