塞来昔布对老年大鼠骨质疏松性骨折愈合过程中转化生长因子β_1的影响

目的探讨塞来昔布(Celecoxib)对老年大鼠骨质疏松性骨折早期愈合过程中转化生长因子(TGF)-β1的影响。方法选用22月龄老年雄性SD大鼠60只,经随机抽取10只测出全身骨密度,与随机抽取的10只12月龄雄性SD大鼠的骨密度对比并做统计学分析,数值降低(P<0.05),确立老年大鼠骨质疏松模型。将老年大鼠制成左股骨骨折模型,随机分为对照组和Celecoxib组,Celecoxib组于术后给予Celecoxib 3 mg·kg-1·d-1灌胃,对照组给予同体积0.9%氯化钠注射液灌胃,共10d。术后在不同阶段处死,取骨痂进行苏木素-伊红(HE)染色、TGF-β1免疫组织化学染色观察及免疫组织化学图像分析。结果HE染色:塞来昔布组软骨生成及软骨内成骨过程较对照组延迟;TGF-β1免疫组织化学染色:两组TGF-β1表达的定位无差别,经图像分析,塞来昔布组在各个时间段TGF-β1蛋白阳性表达的积分吸光度(IA)值均弱于对照组,差异有统计学意义。结论塞来昔布通过抑制TGF-β1的表达,延缓老年大鼠骨质疏松性骨折的愈合。

Effects of Celecoxib on expression of TGF-β1 during the healing process of osteoporotic fracture in aged rats

Objective To investigate the effects of Celecoxib on expression of TGF-β1 during the early healing process of osteoporotie fracture in aged rats. Methods The status of osteoporosis in 22-month-old male rats was confirmed by total body bone mineral density measurement. Fracture healing model was established by osteotomy with a wire saw and fixation with a Kirschner wire on left lemur. Sixty model rats were randomized into two groups： 30 for control group, and 30 for Celecoxib group. Celecoxib group was given daily by garage at dose of 3 mg/kg for a total of 10 days, while control group was given an equivalent volume of saline. The rats were sacrificed in batches at 3 days, 1, 2, 3, 4, 8 weeks after operation, and the callus formation was examined with histological and immunohistochemistry （transforming growth factor beta 1,TGF-beta 1） assessment. Results Histomorphological analysis revealed delayed cartilage formation and transformation in Celecoxib group. Immunohistochemical localization showed comparable levels of TGF-β1 expression in the two groups. By the image analysis, the Celecoxib group showed lower integral optical density of TGF-β1 protein expression at all time spots as compared with the control group, with a statistically significant difference. Conclusion Celecoxib may delay the osteoporotic fracture healing in aged rats by inhibiting TGF-β1 expression.