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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 effects of selective and non-selective cyclooxygenase 2 (COX2) inhibitors on the prevention of heterotopic ossification after ruptured Achilles tendon in rats, and to provide a reference for clinical choice of preventing heterotopic ossification. Methods Fifty male Sprague-Dawley rats aged 6 to 8 weeks, weighing 190.0 ± 8.5 g, were randomly divided into 5 groups with 10 rats in each group. From the first day after operation, celecoxib 2 and 10 mg / kg · d were given to rats in groups A and B, indomethacin 2 and 10 mg / (kg · d) Group given 2 mL saline daily for 10 weeks. The general situation of the rats was observed after surgery. The right hind limb radiographs were taken at 5 and 10 weeks to observe the new bone formation. The 10-week histological examination of the right Achilles tendon was performed, and the heterotopic ossification was evaluated by X-ray. The expression of COX2 and BMP-2 in the Achilles tendon was evaluated by immunohistochemical staining. Results A total of 5 rats died during the experiment, including 2 in group B, 1 in group C and 2 in group D; all other rats survived until the experiment was completed. The general observation showed that the volume of Achilles tendon was the smallest in group B, the texture was soft and no cartilage-like tissue. The size of Achilles tendon tissue was the largest in group E, and the cartilage-like tissue was seen. Combined with X-ray and histological findings, the incidence of heterotopic ossification in group A was 80.0% (8/10) at 10 weeks after operation, 25.0% (2/8) in group B and 88.9% (8 / (P = 0.002, P = 0.023) in group B, group D compared with group C (P = 0.002, P = 0.023) P = 0.015), the differences were statistically significant; the other groups were no significant difference (P> 0.05). Immunohistochemical staining showed that the expression of COX2 in group B and group D was significantly lower than that in group E (P <0.05), and there was no significant difference among the other groups (P> 0.05). The expression of BMP-2 in group B was significantly lower There were no significant differences among the other groups (P> 0.05) in groups A, C and E (P <0.05). Conclusion The administration of celecoxib at a dose of 10 mg / (kg · d) can effectively reduce the incidence of heterotopic ossification after ruptured Achilles tendon in rats.