长期应用糖皮质激素对大鼠股骨头骨组织骨保护素/NF-κB受体活化因子配基-基质金属蛋白酶/基质金属蛋白酶组织抑制剂系统的影响  

EFFECT OF GLUCOCORTICOID ON EXPRESSION LEVELS OF OSTEOPROTEGERIN/RECEPTOR ACTIVATOR OF NUCLEAR FACTOR KAPPA B LIGAND-MATRIX METALLOPROTEINASE/TISSUE INHIBITOR OF MATRIX METALLOPROTEINASE SYSTEM IN BONE TISSUES OF FEMORAL HEAD OF RATS

作　　者：王建忠[1] 王坤正[2] 周荣兴[1] 李晓东[1] 郭军[1] 杨铁翼[1] 吕慧成[1] 

机构地区：[1]内蒙古医学院第二附属医院骨外科,呼和浩特010030 [2]西安交通大学医学院第二附属医院骨外科

出　　处：《中国修复重建外科杂志》2011年第4期402-407,共6页Chinese Journal of Reparative and Reconstructive Surgery

摘　　要：目的观察长期应用糖皮质激素对大鼠股骨头骨组织中骨保护素(osteoprotegerin,OPG)/NF-κB受体活化因子配基(receptor activator of NF-κB ligand,RANKL)-基质金属蛋白酶(matrix metalloproteinase,MMP)/基质金属蛋白酶组织抑制剂(tissue inhibitor of matrix metalloproteinase,TIMP)系统的影响,探讨其导致股骨头缺血性坏死(avascular necrosis of femoral head,ANFH)的相关机制。方法健康SD大鼠40只,雌雄各半,体重250～300g;随机分为高、中、低剂量激素组和对照组,每组10只。高、中、低剂量激素组动物分别给予肌肉注射醋酸泼尼松龙25.0、12.5、7.0mg/kg,每周2次,共4周;对照组给予等量生理盐水。注射期间观察大鼠一般情况,于4周注射完毕后取各组大鼠左侧股骨头行组织学观察,鉴定骨坏死情况;取右侧股骨头骨组织提取总RNA,RT-PCR检测OPG、RANKL、MMP-2、MMP-9、TIMP-1、TIMP-2mRNA表达水平。结果注射醋酸泼尼松龙后高剂量激素组4只、中剂量激素组1只于第23～26天因饮食减少、体重下降最终致全身衰竭死亡。HE染色可见各激素组骨小梁和骨单位完整性不同程度破坏,形成不连续的骨碎片,部分骨陷窝内骨细胞消失,被炎性肉芽组织取代;对照组可见骨单位完整,板层围绕血管呈同心圆排列,大多数骨小梁陷窝内可见骨细胞。高、中、低剂量激素组及对照组ANFH发生率分别为83.3%(5/6)、66.7%(6/9)、30.0%(3/10)、0(0/10)。RT-PCR检测示,各激素组与对照组比较,OPG、TIMP-1、TIMP-2mRNA表达均降低,差异有统计学意义(P<0.05),并且随激素用量增加呈下降趋势;各激素组间OPG mRNA表达差异有统计学意义(P<0.05);中、低剂量激素组间TIMP-1、TIMP-2mRNA表达比较差异无统计学意义(P>0.05),但明显高于高剂量激素组(P<0.05)。各激素组与对照组比较,RANKL、MMP-2、MMP-9mRNA表达均增高,并且随激素用量增加呈上升趋势,其中高、中剂量激素组显著高于对照组(P<0.05);高、�Objective To investigate the effect of glucocorticoid on the expression levels of osteoprotegerin（OPG）/receptor activator of nuclear factor kappa B ligand（RANKL）-matrix metalloproteinases（MMP）/tissue inhibitor of matrix metalloproteinase（TIMP） system in bone tissues of femoral head of rats,and to discuss its interrelated action mechanism in glucocorticoid-induced avascular necrosis of femoral head（ANFH）.Methods Forty adult Sprague Dawley rats,weighing 250-300 g,half males and half females,were randomly divided into 4 groups：high dose glucocorticoid group（HD,n=10）,medium dose glucocorticoid group（MD,n=10）,low dose glucocorticoid group（LD,n=10）,and control group（n=10）.The rats in HD group,MD group,and LD group were intramuscularly injected with 25.0,12.5,and 7.0 mg/kg of prednisolone respectively,and the rats in the control group were injected with physiological saline.After 4 weeks intervention,the osteonecrosis of left femoral heads was observed by HE staining,total RNA was extracted from the right femoral head bone tissue and the mRNA expression levels of OPG,RANKL,MMP-2,MMP-9,TIMP-1,and TIMP-2 were detected by RTPCR.Results After injection of prednisolone,4 rats of HD group and 1 rat of MD group died of systemic failure caused by the decreased food and weight culminating in cachexia.HE staining showed that the integrity of bone trabecula and osteon was destroyed at different levels,discontinuous bone chips formed,and osteocytes were replaced by granulation tissue in some lacunae in HD,MD,and LD groups;the integrated osteon was observed,the lamellar structure formed concentric circles around the blood vessel and osteocytes were seen in the lacunae in the control group.The necrosis rates of femoral head were 83.3%（5/6）,66.7%（6/9）,30.0%（3/10）,and 0（0/10） in HD,MD,LD,and control groups.The results of RT-PCR showed：the mRNA expression levels of the OPG,TIMP-1,TIMP-2 in HD,MD,and LD groups were lower than those in the control group,showing significant difference

关 键 词：糖皮质激素 股骨头缺血性坏死 骨保护素 NF-κB受体活化因子配基 基质金属蛋白酶 基质金属蛋白酶组织抑制剂 大鼠 

分 类 号：R681.8[医药卫生—骨科学]