[选择性和非选择性环氧化酶2抑制剂对跟腱切断大鼠模型异位骨化的影响]

Wu Jiang, Xiao Haijun, Xue Feng, Shi Weizhe, Zhao Hang

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2014 Mar;28(3):371-6.

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 x d)] and B [10 mg/(kg x d)], indomethacin in groups C [(2 mg/(kg x d) and D [10 mg/(kg x 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). COX2 expression level in groups B and D was significantly lower than that in group E (P < 0.05 ), but no significant difference was found among the other groups (P > 0.05); BMP-2 expression level in group B was significantly lower than that in groups A, C, and E (P < 0.05), but no significant difference was found among the other groups (P > 0.05).

CONCLUSION

Celecoxib at a dose of 10 mg/(kg x d) can effectively reduce the incidence of heterotopic ossification in rats.

目的

比较选择性环氧化酶2（COX2）抑制剂与非选择性COX2抑制剂药物在大鼠模型中预防异位骨化的疗效，为临床预防异位骨化药物的选择提供参考。

方法

选取50只6至8周龄、体重（190.0±8.5）g的雄性Sprague Dawley大鼠；切断右侧跟腱诱导异位骨形成。将大鼠随机分为5组（n = 10）：建模后第1天，A组[2 mg/（kg·d）]和B组[10 mg/（kg·d）]给予塞来昔布，C组[2 mg/（kg·d）]和D组[10 mg/（kg·d）]给予吲哚美辛，E组给予2 mL生理盐水，持续10周。术后观察大鼠一般情况。术后5周和10周，拍摄右下肢X线片观察新骨形成情况。术后10周，取右侧跟腱组织进行组织学观察。根据X线和组织学结果评估异位骨化情况。采用免疫组织化学染色评估局部跟腱中COX2和骨形态发生蛋白2（BMP - 2）的表达水平。

结果

实验期间，5只大鼠死亡（B组2只，C组1只，D组2只），其余大鼠存活至实验结束。跟腱组织大体观察显示，B组肌腱组织体积最小，质地柔软，无软骨样组织；E组肌腱组织体积最大，质地坚硬，有软骨样组织。术后10周，A - E组异位骨化发生率分别为80.0%（8/10）、25.0%（2/8）、88.9%（8/9）、50.0%（4/8）和100%（10/10）；B组、D组与E组之间（P = 0.002，P = 0.023）以及B组与C组之间（P = 0.015）差异有统计学意义，其他组之间差异无统计学意义（P > 0.05）。B组和D组COX2表达水平显著低于E组（P < 0.05），其他组之间差异无统计学意义（P > 0.05）；B组BMP - 2表达水平显著低于A组、C组和E组（P < 0.05），其他组之间差异无统计学意义（P > 0.05）。