摘要
背景:糖皮质激素性骨质疏松的发生机制与骨保护蛋白表达下调相关,在治疗雌激素缺乏性骨质疏松的动物实验和临床应用中,骨保护蛋白均表现出良好的抗骨吸收效能。目的:验证外源性重组骨保护蛋白对糖皮质激素所致骨质疏松的影响。设计、时间及地点:随机分组设计、对照动物实验,于2006-01/2008-06在解放军总医院骨科研究所完成。材料:选择清洁级健康成年雄性wistar大鼠60只;地塞米松磷酸钠注射液为天津金耀氨基酸有限公司产品,批准文号:国药准字H12020515。方法:大鼠随机分为3组,每组20只。对照组,生理盐水给药对照组;地塞米松组,单纯糖皮质激素给药组;骨保护蛋白组,糖皮质激素联合重组骨保护蛋白给药组。主要观察指标:12周各组大鼠分别取材,进行尿钙、磷、肌酐、骨密度、骨生物力学测定;大鼠骨骼局部免疫组织化学染色观察骨保护素表达。结果:纳入动物60只,均进入结果分析。①地塞米松组与对照组比较,尿钙上升(P<0.05);腰椎、股骨骨密度均明显下降(P<0.05),其中腰椎骨密度下降尤为显著(P<0.01);腰椎和股骨生物力学检测最大载荷、最大应力、弹性载荷、弹性应力、弹性模量显著下降(P<0.05);免疫组织化学显示骨髓内源性骨保护蛋白表达显著下降(P<0.01)。②骨保护蛋白组与地塞米松组比较,尿钙下降(P<0.01);骨密度增加(P<0.05);腰椎和股骨生物力学检测指标均增强(P<0.05);骨髓内源性骨保护蛋白表达无明显变化。结论:糖皮质激素抑制骨骼局部骨保护蛋白表达,继发了渐进性骨质丢失,促进了骨质疏松的形成。重组骨保护蛋白可以部分抑制糖皮质激素引起的骨吸收,降低骨吸收指标、提高骨密度、增加骨强度,从而改善糖皮质激素性骨质疏松状况。
BACKGROUND： Glucocorticoid-induced osteoporosis has relationship with the down-regulation of osteoprotegerin expression. Osteoprotegerin could inhibit bone resorption in the animal experiment and clinical application for treating oestrogenic hormone deficiency osteoporosis. OBJECTIVE： To investigate the effects of exogenous recombinant osteoprotegerin fusion protein on glucocorticoid-induced osteoporosis in rats. DESIGN, TIME AND SETTING： Randomized grouping, controlled animal experiment was performed in the Institute of Orthopedics, Chinese PLA General Hospital between January 2006 and June 2008. MATERIALS： Sixty healthy male Wistar rats of clean grade; Dexamethasone was produced by Tianjin Jinyao Amino Acid Co., Ltd （Licence No. H12020515）. METHODS： Sixty rats were divided into 3 groups randomly with 20 rats in each. Control group： the rats were administrated with 0,9% sodium chloride. Dexamethasone group： the rats were administrated with dexamethasone intramuscularly. Osteoprotegerin group： the rats were administrated with dexamethasone and recombinant osteoprotegerin intramuscularly. MAIN OUTCOME MEASURES： All rats were sacrificed at 12 weeks after administration. The urine calcium, phosphor, creatinine, bone mineral density, biomechanics tests of femur and vertebral body, were measured. Immunohistochemistry staining were performed to observe osteoprotegerin expression. RESULTS： Sixty rats were all involved in the final analysis, （1）Compared with control group, urine calcium increased in the Dexamethasone group （P 〈 0.05）; the bone mineral density of lumbar vertebra and femur decreased significantly （P 〈 0.05）, especially lumbar vertebra （P 〈 0.01 ）; biomechanics tests of femur and vertebral body （maximum load, maximum stress, elasticity load, elasticity stress, elastic modulus） decreased significantly （P 〈 0.05）; immunohistochemistry staining showed that endogenous osteoprotegerin expressions were reduced significantly in bone marrow of Dexamethasone gr
出处
《中国组织工程研究与临床康复》
CAS
CSCD
北大核心
2009年第28期5470-5474,共5页
Journal of Clinical Rehabilitative Tissue Engineering Research
基金
北京市科技新星计划(2007B070)~~
