青藤碱关节腔注射对膝骨关节炎兔软骨和滑膜组织形态学及基质金属蛋白酶—13和软骨寡聚基质蛋白的影响

郑洁+王瑞辉+寇久社

摘要：目的 观察青藤碱关节腔注射对膝骨关节炎模型兔关节软骨和滑膜组织形态学及血清和关节液中基质金属蛋白酶（MMP）-13和软骨寡聚基质蛋白（COMP）含量的影响，探讨青藤碱治疗膝骨关节炎的部分作用机制。方法 38只新西兰大白兔随机分为空白组、模型组、透明质酸钠组和青藤碱组。空白组不予任何处理，模型组、透明质酸钠组和青藤碱组通过木瓜蛋白酶关节腔注射法诱导膝骨关节炎模型后，分别用生理盐水、透明质酸钠和青藤碱干预。5周后取关节软骨及滑膜HE染色并进行组织学评分，ELISA检测血清及关节液中MMP-13和COMP的含量。结果 模型组软骨Mankin's评分和滑膜组织病理学评分显著高于空白组，青藤碱组软骨Mankin's评分和滑膜组织病理学评分显著低于模型组（P<0.01）；模型组血清及关节液中MMP-13和COMP含量较空白组显著升高（P<0.01）；青藤碱组血清、关节液中MMP-13含量较模型组显著降低，关节液中COMP含量较模型组降低（P<0.05，P<0.01）。结论 青藤碱具有改善滑膜炎症、延缓关节软骨退变进程的作用。

关键词：青藤碱；骨关节炎；形态学；基质金属蛋白酶-13；软骨寡聚基质蛋白；兔

DOI：10.3969/j.issn.1005-5304.2016.01.017

中图分类号：R285.5 文献标识码：A 文章编号：1005-5304（2016）01-0074-04

Effects of Intra-articular Injection of Sinomenine on Morphology， MMP-13 Level and Cartilage Oligomeric Matrix Protein of Rabbit Knee Osteoarthritis Model ZHENG Jie1， WANG Rui-hui1， KOU Jiu-she2 （1. College of Acupunture and Moxibustion， Shaanxi University of Chinese Medicine， Xianyang 712046， China； 2. Second Affiliated Hospital of Shaanxi University of Chinese Medicine， Xianyang 712046， China）

Abstract： Objective To observe the effects of intra-articular injection of sinomenine on morphology of synovium and cartilage as well as contents of MMP-13 and cartilage oligomeric matrix protein （COMP） in serum and synovial fluid of rabbit knee osteoarthritis model. Methods A total of 38 New Zealand white rabbits were randomly divided into 4 groups： control group， model group， hyaluronate group and sinomenine group. Model group， hyaluronate group and sinomenine group established knee osteoarthritis model by intra-articular injection of papain enzyme， and were treated with saline， sodium hyaluronate and sinomenine respectively except for control group. 5 weeks after treatment， all rabbits were sacrificed for HE staining and histological grading on cartilago articularis and synovium， and ELISA method was used to detect the contents of MMP-13 and COMP in rabbit serum and synovial fluid. Results Mankin's scores of articular cartilage and histological scores of synovium in model group were significantly higher than those of control group （P<0.01）， and were markedly lower in sinomenine group than those of model group （P<0.01）； the contents of MMP-13 and COMP in serum and synovial fluid of model group were significantly raised compared with control group （P<0.01）， and were reduced obviously in sinomenine group compared with model group （P<0.05， P<0.01）. Conclusion Intra-articular injection of sinomenine can reduce the levels of MMP-13 and COMP in serum and synovial fluid of rabbit knee osteoarthritis model， and improve synovial inflammation， as well as delay the degradation of articular cartilage.

Key words： sinomenine； osteoarthritis； morphology； MMP-13； cartilage oligomeric matrix protein； rabbits

骨性关节炎（osteoarthritis，OA）是一类以关节软骨细胞外基质进行性破坏为特点，并伴有滑膜、软骨下骨及关节周围组织病变的复杂性关节疾病。由于病理机制不明确，目前无有效方法可完全阻止OA的病理进程。青藤碱是从中药青风藤中提取的一种生物碱，具有镇痛、抗炎、调节免疫、降血压、抗心律失常等药理作用[1]。青藤碱在骨关节病中的临床及实验研究目前仍主要集中在类风湿关节炎，而应用于OA的研究较少。本实验通过观察盐酸青藤碱关节腔注射对膝骨关节炎模型兔软骨……