【作者】 段圆慧；

【导师】 尹芸生；

【作者基本信息】 山西医科大学 ， 骨外科学， 2008， 硕士

【摘要】 目的探讨塞来昔布（Celecoxib）对老年大鼠骨质疏松性骨折愈合过程的影响。方法选用22月龄老年雄性SD大鼠70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,直径1.5mm克氏针髓内固定。随机分为对照组和Celecoxib组,Celecoxib组于术后给予塞来昔布（Celecoxib）3mg/kg体重/d灌胃,对照组给予同体积0.9%氯化钠注射液灌胃,共10天。两组均在术后3d、1w、2w、3w、4w、8w各随机处死5只,取骨痂,4%多聚甲醛固定24小时,20%EDTA（PH=8.0）脱钙5周,切片,行HE染色、TGF-β₁免疫组织化学染色观察及免疫组化图像分析;并于2w、4w、8w和12w测骨痂骨密度及4w、8w和12w测右侧股骨骨密度;1w、2w、4w、8w和12w测定血清钙、磷及碱性磷酸酶（ALP）;12w行放射学（X线片）观察。所得到的计量数据以均数±标准差表示,实验组与对照组均数间比较采用两样本资料的t检验,P＜0.05为差别有统计学意义。结果1.组织学观察: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光密度（IOD）值均弱于对照组,差别有统计学意义;2.骨密度:塞来昔布组各时间段骨痂骨密度均较对照组降低,差别有统计学意义;两组各时间段右侧股骨骨密度的差别无统计学意义;3.钙磷乘积、碱性磷酸酶（ALP）:塞来昔布组ALP较对照组减低,差别有统计学意义,钙磷乘积两组的差别无统计学意义;4.放射学观察:对照组术后12w骨折线变模糊,骨痂连接断端,髓腔再通;塞来昔布组术后12w骨折线仍较清晰,断端骨痂连接不紧密。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。更多还原

【Abstract】 ObjectiveTo investigate the effects of Celecoxib on osteoporotic fracture healing in aged rats.MethodsThe 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 pin on left femur.70 model rats were randomized into two groups:35 for control group,and 35 for Celecoxib group.Celecoxib group was given daily by gastric gavage at dose of 3mg/kg for total 10 days,while control group was given an equivalent volume of saline.The rats were scarified in 3 days,1,2,3,4,8 and 12 weeks after operation,the callus formation was monitored by histological and immunohistochemistry(transforming growth factor beta 1,TGF-beta 1) assessment,the bone mineral density measurement of the callus and the right femur was taken,alkaline phosphatase(ALP) activity as an index of bone formation was arrayed.Normal radiographs were taken at 12 weeks.Get the measurement data to mean±standard deviation,the experimental group and the control group were few compared with the two samples of information t test,P＜0.05 for the difference statistically significant.Results1.The histomorphological analysis revealed that the process of cartilage forming and transforming were postponed in Celecoxib group.The immunohistochemical results showed a decrease of expression of TGF-betal in Celecoxib group.2.Celecoxib group had lower bone mineral density.3.Celecoxib produced a significant decrease in serum ALP.4.Normal radiographs showed Celecoxib group had less callus formation.ConclusionCelecoxib delays the osteoporotic fracture healing in aged rats.The most contributing factor associated with the poor fracture healing was inhibition of TGF-beta 1.更多还原