选择性与非选择性环氧化酶2抑制剂预防大鼠跟腱异位骨化的实验研究  

EFFECTS OF SELECTIVE AND NON-SELECTIVE CYCLOOXYGENASE 2 INHIBITORS ON HETEROTOPIC OSSIFICATION IN RAT MODEL WITH Achilles TENOTOMY

作　　者：吴江[1,2] 肖海军[1,2] 薛锋[1,2] 石伟哲[1,2] 赵航[1,2] 

机构地区：[1]南方医科大学第三临床医学院 [2]南方医科大学附属奉贤医院骨科,上海201400

出　　处：《中国修复重建外科杂志》2014年第3期371-376,共6页Chinese Journal of Reparative and Reconstructive Surgery

摘　　要：目的 比较选择性与非选择性环氧化酶2（cyclooxygenase 2，COX2）抑制剂预防大鼠跟腱断裂后异位骨化的作用，为临床选择预防异位骨化药物提供参考。 方法 取6～8周龄雄性SD大鼠50只，体重（190.0 ± 8.5） g，切断右后肢跟腱制备跟腱异位骨化模型；随机分为5组，每组10只。术后第1天开始，A、B组分别给予塞来昔布2、10 mg/ （kg·d），C、D组分别给予吲哚美辛2、10 mg/（kg·d），E组每天给予2 mL生理盐水，共10周。术后观察大鼠一般情况，于5、10周摄右后肢侧位X 线片，观察新骨形成情况。10周取右侧跟腱行组织学观察，并结合X线片结果评定异位骨化形成情况；免疫组织化学染色评价COX2和BMP-2在跟腱局部表达水平。 结果 实验期间共5只大鼠死亡，其中B组2只、C组1只、D组2只；其余大鼠均存活至实验完成。大体观察示B组跟腱组织体积最小、质地软，无软骨样组织；E组跟腱组织体积最大、质地硬，可见软骨样组织。 结合X线片及组织学观察结果，术后10周A组异位骨化发生率为80.0%（8/10），B组为25.0%（2/8），C组为88.9%（8/9），D组为50.0%（4/8），E组为100%（10/10）；B、D组与E组比较（P=0.002，P=0.023）、B组与C组比较（P=0.015），差异均有统计学意义；其余各组间比较，差异均无统计学意义（P 〉 0.05）。免疫组织化学染色示，B、D组COX2表达量显著低于E组（P 〈 0.05），其余各组间比较差异均无统计学意义（P 〉 0.05）；B组BMP-2表达量显著低于A、C、E组（P 〈0.05），其余各组间比较差 异无统计学意义（P 〉 0.05）。 结论 按照10 mg/（kg·d）剂量给予塞来昔布能有效降低大鼠跟腱断裂后异位骨化发生率。Objective To compare the efficacy of selective cyclooxygenase 2 （COX2） inhibitor and non-selective COX2 inhibitor drugs in prevention of heterotopic ossification in rats model so as to provide reference for clinical drugs selection of heterotopic ossification prevention. Methods Fifty male Sprague Dawley rats, 6 to 8 weeks old, weight （190.0 ± 8.5） g, were selected; the right Achilles tendon was cut off to induce ectopic bone formation. The rats were randomly divided into 5 groups （n=10）： on the 1st day after modeling, celecoxib was given in groups A [2 mg/（kg·d）] and B [10 mg/（kg·d）], indomethacin in groups C [（2 mg/ （ kg·d） and D [10 mg/（kg·d）], and 2 mL of saline in group E for 10 weeks. The general condition of rats was observed after operation. At 5 and 10 weeks after operation, X-ray films of the right lower limb were taken to observe new bone formation. At 10 weeks after operation, the right Achilles tendon tissue was harvested for histological observation. Based on X-ray and histological results, heterotopic ossification was assessed. Immunohistochemical staining was used to evaluate COX2 and bone morphogenetic protein 2 （BMP-2） expression levels in local Achilles tendon. Results During the experiment, 5 rats died （2 in group B, 1 in group C, and 2 in group D）, the other rats survived to the end of the experiment. General observation of Achilles tendon tissue showed that the tendon tissue volume of group B was the smallest, with soft texture and no cartilage-like tissue; the tendon tissue volume of group E was the biggest, with hard texture and cartilage-like tissue. The incidence of heterotopic ossification was 80.0 % （8/10）, 25.0% （2/8）, 88.9% （8/9）, 50.0% （4/8）, and 100% （10/10） in groups A-E respectively at 10 weeks after operation; significant differences were found between groups B, D and group E （P=0.002, P=0.023） and between groups B and C （P=0.015）, but no significant difference was found among the other groups （P 〉 0.05

关 键 词：异位骨化 选择性环氧化酶2抑制剂 非选择性环氧化酶2抑制剂 大鼠 

分 类 号：R686.1[医药卫生—骨科学]