塞来昔布对创伤性异位骨化跟腱组织相关因子表达及生物力学的影响  

Effect of celecoxib on the expression of related factors and biomechanics of Achilles tendon in traumatic heterotopic ossification

作　　者：冯祁军 蒋毅 FENG Qijun;JIANG Yi(Department of Orthopedics,the First Hospital of Jiaxing,Jiaxing 314001,China)

机构地区：[1]嘉兴市第一医院骨科,314001

出　　处：《浙江医学》2024年第17期1797-1803,共7页Zhejiang Medical Journal

基　　金：嘉兴市重点实验室(2022-yzcsgtjzjz);嘉兴市重点学科(2023-ZC-012);嘉兴市第一医院院级课题(2021-YA-071)。

摘　　要：目的探讨塞来昔布对创伤性异位骨化(HO)跟腱组织相关因子表达及生物力学的影响。方法采用随机数字表法将60只实验兔分为正常组、模型组、塞来昔布低剂量组、塞来昔布高剂量组、塞来昔布用药3周组、塞来昔布用药6周组,每组10只。除正常组外,其余实验兔均建立创伤性HO模型。造模成功后,塞来昔布低、高剂量组分别给予塞来昔布20、60 mg/(kg·d)灌胃,连续10 d;塞来昔布用药3周组给予塞来昔布10 mg/(kg·d)灌胃,连续3周;塞来昔布用药6周组给予塞来昔布10 mg/(kg·d)灌胃,连续6周;正常组与模型组均给予0.9%氯化钠溶液2 mL灌胃,连续10 d。使用ELISA试剂盒检测血清CRP水平;使用皮温计记录肢体皮温,以肢体肿胀评分评估肿胀程度;X线摄片观察新骨形成情况;采用三点弯曲实验法检测兔右跟腱生物力学参数;采用qRT-PCR检测跟腱组织骨形成蛋白(BMP)-2、BMP-4;免疫组化法检测跟腱组织环氧合酶-2(COX-2);Western blot法检测跟腱组织转化生长因子-β(TGF-β)1、Smad1蛋白表达水平。结果与正常组比较,模型组血清CRP水平、平均皮温、肿胀程度及新骨形成评分、跟腱组织BMP-2、BMP-4 mRNA表达水平、COX-2灰度值和TGF-β1、Smad1蛋白表达水平均升高(均P<0.05),而右跟腱最大载荷、抗弯强度、弹性载荷及刚性系数均降低(均P<0.05);与模型组比较,塞来昔布低、高剂量组及塞来昔布用药3、6周组血清CRP水平、平均皮温、肿胀程度及新骨形成评分,跟腱组织BMP-2、BMP-4 mRNA表达水平,COX-2灰度值和TGF-β1、Smad1蛋白表达水平均降低(均P<0.05),而右跟腱最大载荷、抗弯强度、弹性载荷及刚性系数均升高(均P<0.05);与塞来昔布低剂量组比较,塞来昔布高剂量组血清CRP水平、平均皮温、肿胀程度及新骨形成评分、跟腱组织BMP-2、BMP-4 m RNA表达水平、COX-2灰度值和TGF-β1、Smad1蛋白表达水平均降低(均P<0.05);塞来昔布用药3、6�Objective To investigate the effect of celecoxib on the expression of related factors and biomechanics of Achilles tendon in traumatic heterotopic ossification(HO).Methods A total of 60 rabbits were divided into normal group,model group,celecoxib low-dose group,celecoxib high-dose group,celecoxib 3-week treatment group,and celecoxib 6-week treatment group,with 10 rabbits in each group.The traumatic HO model was established in all rabbits except those in the normal group.After successful modeling,celecoxib low-dose and high-dose groups were given 20 and 60 mg/(kg·d)celecoxib by gavage,for continuous 10 days,respectively.Celecoxib 3-week and 6-week treatment groups were given 10 mg/(kg·d)celecoxib by gavage for continuous 3,and 6 weeks,respectively.Normal group and model group were both given 2 mL 0.9%sodium chloride solution by gavage for continuous 10 days.Serum CRP levels were detected by ELISA kit.The skin temperature of limbs was recorded by skin thermometer,and the swelling degree was evaluated by limb swelling score.X-ray film was taken to observe the new bone formation.The biomechanical parameters of the right Achilles tendon of rabbits were measured by three-point bending test.Bone morphogenetic protein(BMP)-2 and BMP 4 in Achilles tendon were detected by qRT-PCR.Cyclooxygenase 2(COX 2)of Achilles tendon was detected by immunohistochemistry.The expression levels of transforming growth factor-β(TGF-β)1 and Smad1 in Achilles tendon tissues were detected by Western blot method.Results Compared with normal group,serum CRP level,average skin temperature,swelling degree and new bone formation score,mRNA expression levels of BMP 2 and BMP 4 in Achilles tendon tissue,gray value of COX 2,and protein expression levels of TGFβ1 and Smad1 in model group were increased(all P<0.05).The maximum load,flexural strength,elastic load,and rigidity coefficient of the right Achilles tendon were decreased(all P<0.05).Compared with model group,the above indicators were all decreased in celeoxib low-and high dose groups and c

关 键 词：塞来昔布 创伤性异位骨化 环氧合酶-2 骨形成蛋白 

分 类 号：R681[医药卫生—骨科学]