间断性低剂量应用重组人甲状旁腺素（1—34）在骨折愈合早期促Runx2基因的表达  

Intermittent low-dose administration of recombinant human parathyroid hormone （1-34） promotes the expression of Runx2 during early stage of fracture healing

作　　者：李宁[1] 王满宜[1] 贺良[1] 姜旭[2] 吴成爱[3] 

机构地区：[1]北京大学第四临床学院(北京积水潭医院)创伤骨科,100035 [2]北京大学第四临床学院(北京积水潭医院)矫形骨科,100035 [3]北京市创伤骨科研究所

出　　处：《中华医学杂志》2009年第11期771-776,共6页National Medical Journal of China

摘　　要：目的研究间断性低剂量应用重组人甲状旁腺素（1-34）[rhPTH（1-34）]在骨折愈合的早期过程中与成骨基因Runx2表达的相关性。方法应用2月龄雄性Sprague—Dawley大鼠建立单侧闭合性股骨骨折内固定模型，随机分为甲状旁腺素治疗组和对照组，术后分别皮下注射重组人甲状旁腺素（1．34）10μg·k^-1·d^-1或等剂量安慰剂，分别于术后第2、4、7、14和21天取双侧股骨标本，提取组织RNA和蛋白质，分别行实时荧光定量PCR和免疫印迹检测，以检测Runx2的mRNA表达和蛋白质水平。结果甲状旁腺素组较对照组，骨折端Runx2的mRNA表达水平于骨折术后第14、21天有明显升高（分别为2．6倍和3．8倍，P〈0．05），同时骨折端Runx2的蛋白质水平也于术后第14、21天时有明显增加。结论间断性低剂量应用重组人甲状旁腺素（1-34）在骨折愈合的早期过程中，可上调成骨基因Runx2的mRNA表达和蛋白质水平，促进骨折的愈合。Objective To study the correlation of intermittent low-dose administration of recombinant human parathyroid hormone （1-34） [ rhPTH （1-34） ] and the expression of Runx2 during early stage of fracture healing. Method Sixty 2-month old male Sprague-Dawley rats underwent close unilateral femoral fracture and intramedullary nail fixation, and then were randomly divided into 2 equal groups： treatment group undergoing subcutaneous injection of rhPTH （1-34） 10 μg · kg^- 1 · d^-1 immediately after the operation, and control group undergoing subcutaneous injection of normal saline of the same dose, Six rats from each group were killed with their bilateral femurs taken out on days 2, 4, 7, 14, and 21 after the operation to undergo X-ray photography Tissue RNA and protein were extracted from the bone tissues and the levels of Runx2 mRNA and protein expression were evaluated through real time quantitative PCR and Western-blotting. Blood samples were collected from the abdominal aorta before the rats were killed to undergo detection of serum calcium, phosphorus, and alkaline phosphatase （AKP）. Results The Runx2 mRNA levels in the fractured femurs of the rhPTH （1-34） group on days 14 and 21 after the operation were 2. 6 and 3.8 times as those of the control group respectively （ both P 〈 0. 05 ）. The Runx2 protein levels in the fractured femurs of the rhPTH （1-34） group on days 14 and 21 after the operation were significantly higher than those of the control group respectively too. Since day 14 fracture healing was seen, and the status of fracture healing was better in the rhPTH （1-34） group than in the control group on days 14 and 21. The levels of serum calcium ion on days 14 and 21 of the rhPTH （1-34） group were both significantly higher than those of the control group （ both P 〈 0. 05 ）. There were not significant differences in the serum levels of AKP, osteocalcin and collagen type Ⅰ at any time point between the 2 groups. Conclusion Intermittent lowdose administration of r

关 键 词：甲状旁腺激素类 骨折愈合 成骨细胞 基因表达 

分 类 号：R686[医药卫生—骨科学]