多西环素对兔膝关节骨关节炎软骨及滑膜中MMP-3和TIMP-1mRNA表达的影响  

The effects of doxycycline on the mRNA expressions of MMP-3 and TIMP-1 of articular cartilage and synovial membrane in osteoarthrRis

作　　者：朱可为[1] 王万春[1] 

机构地区：[1]中南大学湘雅二医院骨科,长沙410011

出　　处：《中国医师杂志》2012年第8期1038-1041,1045,共5页Journal of Chinese Physician

摘　　要：目的探讨多西环素对骨关节炎软骨退变的保护机制，为临床防治退行性骨关节病、治疗创伤性骨关节炎提供实验依据。方法（1）模型制作：成年新西兰大白兔16只，行右侧膝关节前交叉韧带切断术（ACLT），术后不固定右膝关节。分笼饲养，每笼1只。予以青霉素（40万单位）肌注预防感染，11次／d，注射3d。术后第4天，驱赶实验动物以强制膝关节活动，每天60min，持续30d。术后4周，右膝关节创伤性关节炎模型建立完成。（2）动物分组：将动物随机分为两组，每组8只，实验组注射多西环素[1．33％多西环素溶液0．3ml（总量0．4mg）]，对照组注射生理盐水（0．3m1），所有动物均分笼饲养，不再强制活动。总共注射时间为4周。（3）采集标本及数据分析：用空气栓塞的方法处死所有实验动物，采集髌骨关节面软骨及关节内滑膜标本，应用Brittberg软骨退变分级标准进行大体评分。用RT—PCR的方法检测MMP-3mRNA及TIMP-1mRNA的表达。结果大体评分显示实验组髁软骨评分0级6例，1级2例，髌软骨评分0级5例，1级3例。对照组髁软骨退变程度较轻，髌软骨评分0级2例，I级6例。实验组和对照组中，在术后8周都有MMP-3mRNA及TIMP-1mRNA的表达。实验组MMP-3mRNA表达（1．20±0．32）较对照组（1．97±0．54）明显降低（t=3．47，P〈0．05），而实验组中TIMP-1mRNA表达（3．22±0．42）较之对照组（1．90±0．33）有显著缯强（t=6．99，P〈0。01），两者比较差异均有统计学意义。结论关节内注射多西环素后，抑制了关节软骨和滑膜中MMP-3mRNA的表达、上调TIMP-1mRNA的表达，从而减轻关节软骨退变程度。Objective To investigate the mechanisms regarding protection of doxycycline from articular cartilage cataplasis in osteoarthritis, and provide experimental evidence for prevention and cure of degenerative osteoarthropathy and for treatment of osteoarthritis. Methods （1） Models： Sixteen New Zealand rabbits underwent right anterior cruciate ligament riesction, and fed in each cage. The animals were injected with penicillin 400 thousands IU once a day for 3 days to prevent from infection. On the fourth day after op- eration, the animals were compelled to use their operated knee by driving 60 minutes per day for 4 weeks. （2） Animal groups： the animals were divided into two groups. The animals in experimental group were injec- ted into the knees with 1.33% doxycycline 0. 3 ml （total 0.4 mg）, once a day for 4 weeks. Rabbits in the control group were treated under the same condition using normal saline 0. 3 ml. All rabbits were fed in their own cage and not drove. The total time was 4 weeks. （3）Example collection and data analysis： Rabbits were sacrificed by aeroembolism and their knee joints were examined by gross morphology. The mRNA expres- sions of MMP-3 and TIMP-1 in the cartilage and synovium were analyzed by a reverse transcription polymer- ase chain reaction （RT -PCR）. Results For the experimental group, condyles of femur cartilage inspec-tion revealed that 6 cases were in Grade 0 and 2 cases were in Grade 1, and whirbone cartilage inspection showed that 5 cases were in Grade 0 and 3 cases were in Grade 1. For the control group, 2 cases were in Grade 0 and 6 cases were in Grade 1. The extent of articular cartilage cataplasis was significantly different mRNA expression of MMP-3 （ 1.20±0. 32） （experimental） and （ 1.97 ±0. 54） （compared） （ t = 3.47, P 〈 0. 05 ）. The expression of MMP-3 mRNA in cartilage and synovium was significantly decreased, respec-tively; while the expression of TIMP-1 mRNA was significantly increased in the experimental group（ 3.22±0.42） e

关 键 词：多西环素/药理学 骨关节炎 膝 基质金属蛋白酶3/代谢 金属蛋白酶1组织抑制剂/代谢 

分 类 号：R684.3[医药卫生—骨科学]