选择性环氧化酶2抑制剂对创伤后异位骨化形成的预防作用及对OPG/RANKL信号通路的影响

The preventive effect of selective cyclooxygenase 2 inhibitor on heterotopic ossification after trauma and its effect on OPG/RANKL signaling pathway

目的探讨选择性环氧化酶2抑制剂对创伤后异位骨化的预防作用及对OPG/RANKL信号通路的影响。方法实验兔随机分成对照组(C组)、模型组(M组)和帕瑞昔布低剂量组(P1组)、中剂量组(P2组)、高剂量组(P3组),M、P1、P2及P3组建立异位骨化模型,期间给予生理盐水或帕瑞昔布(4、8、12 mg/kg)。X线评估异位骨化形成情况,免疫组化方法检测OPG、RANKL蛋白的表达,RT-PCR法测定TNF-α、IL-1βm RNA的表达。结果与对照组比较,模型组异位骨化明显增多(P<0.05),TNF-α、IL-1βm RNA及OPG蛋白表达明显增多(P<0.05),OPG/RANKL比值明显增大(P<0.05);与模型组比较,中、高剂量帕瑞昔布组异位骨化明显减少(P<0.05),TNF-α、IL-1βm RNA及OPG蛋白表达明显减少(P<0.05),OPG/RANKL比值明显降低(P<0.05),随着剂量增加减少越明显(P<0.05)。结论 OPG/RANKL信号通路的激活可能是创伤后异位骨化形成的重要因素,中、高剂量帕瑞昔布能降低OPG/RANKL比值,对预防异位骨化有积极作用。

Objeαive To investigate the preventive effeα of seleαive cyclooxygenase 2 inhibitor on heterαopic ossifi- cation after trauma and its effeα on OPG/RANKL signaling pathway. Methods The experimental rabbits were randomly divided into control group（group C）, model group（group M） and parecoxib low dose group（group P1）, medium dose group （group P2）, high dose group（group P3）. M, P1, P2 and P3 groups established heterαopic ossification model. Saline or parecoxib was given（4, 8, 12 mg/kg）. Heterαopic ossification was evaluated by X-ray. Immunohistochemistry was used to deteα the expression of OPG and RANKL prαein, and the expression of TNF-α and IL-lβ mRNA was determined by RT-PCR. Results Compared with the control group, the heterαopic ossification in the model group was increased significantly（P〈O.05）. TNF-α, IL-Iβ mRNA and OPG prαein expression was increased significantly（P〈0.05）. The ratio of OPG/RANKL was increased significantly（P〈0.05）; compared with the model group, the heterαopic ossification in the medium-dose and high-dose parecoxib group was significantly reduced（P〈O.05）. TNF-α, IL-lβ mRNA and OPG prαein expression was decreased significantly（P〈0.05）. OPG/RANKL ratio was significantly lower（P〈0.05）. The decrease was more significant along with the increase of doses（P〈O.05）. Conclusion Aαivation of OPG/RANKL signaling pathway may be an important faαor in the formation of heterαopic ossification after trauma. Medium and high-doses of pare- coxib can reduce the ratio of OPG/RANKL, which has a positive effeα in the prevention of heterαopic ossification.