不同剂量甲状旁腺激素对下颌支截骨术后骨愈合的影响及其机制研究

Expression of osteoprotegerin and receptor activator of nuclear factor kappa-B ligand in mandibular ramus osteotomy healing with administration of different doses of parathyroid hormone

目的探究不同剂量甲状旁腺激素（parathyroid hormone，PTH）对下颌支截骨术后骨愈合的影响及机制。方法建立兔下颌支截骨术模型，将60只新西兰大耳白兔按随机数字表分为实验A、B组及对照组，每组20只。实验A组、B组和对照组术后分别隔日皮下注射PTH 20、40 μg/kg和生理盐水1 ml，在术后第1、2、3、4周行下颌支截骨区新骨的组织形态学研究，锥形束CT检测下颌支截骨区新骨阻射密度及成骨情况。实时荧光定量PCR检测新骨组织中骨保护素和核因子κB受体活化因子配体（receptor activator of nuclear factor kappa-B ligand，RANKL）mRNA的表达量。结果在各时期实验组截骨区新骨成骨质量、骨痂阻射密度均优于对照组，实验B组成骨效应最强。各时期实验A组骨保护素mRNA的表达量（1.127±0.035 1.742±0.049 1.049±0.062，1.063±0.036）均显著高于对照组（0.965±0.082，1.254±0.071，0.793±0.061，0.684±0.055）（P=0.010，P=0.000，P=0.001，P=0.020），实验B组（1.416±0.205，2.648±0.168，1.652±0.091，1.712±0.070）均显著高于实验A组（P=0.000，P=0.010，P=0.023，P=0.003）；对照组RANKL mRNA的表达量（1.666±0.086，1.058±0.105，0.885±0.124，0.972±0.136）均显著高于实验A组（0.788±0.036，0.585±0.017，0.692±0.017，0.527±0.051）（P=0.001，P=0.006，P=0.003，P=0.028）且实验A组均显著高于实验B组（0.247±0.022，0.240±0.034，0.134±0.011，0.103±0.050）（P=0.000，P=0.001，P=0.002，P=0.012）。结论间歇性皮下注射PTH，可上调骨保护素、抑制RANKL的表达，加速骨代谢，促进截骨区新骨形成；40 μg/kg剂量组的成骨效应较20 μg/kg剂量组明显。

Objective To investigate the effect of parathyroid hormone （PTH） on the bone healing of mandibular ramus osteotomy.Methods The mandibular ramus osteotomy model was established in sixty rabbits and these rabbits were randomly divided into experimental group A, experimental group B and control group. In the experimental group A and experimental group B, the rabbits were given PTH （20 and 40 μg/kg respectively） every other day after operation. In the control group, 1 ml saline was given. The animals were sacrificed at 1 week, 2 weeks, 3 weeks and 4 weeks postoperatively. The new bone formation was observed by histology and cone bone CT. The expression of osteoprotegerin and receptor activator of nuclear factor kappa-B （RANKL） in the new bone was detected by real-time quantitative PCR.Results The experimental groups has better osteogenesis and the bone mineral density than the control group in osteotomy area. The experimental group B showed the best osteogenesis.Osteoprotegerin mRNA expression in experimental group A （1.127±0.035, 1.742±0.049, 1.049±0.062, 1.063±0.036） was significantly higher than that in the control group in each period （0.965±0.082, 1.254±0.071, 0.793±0.061, 0.684±0.055） （P=0.010, P=0.000, P=0.001, P=0.020）, while group B （1.416±0.205, 2.648±0.168, 1.652±0.091, 1.712±0.070） was significantly higher than group A （P=0.000, P=0.010, P=0.023, P=0.003）. RANKL mRNA expression in control group （1.666±0.086, 1.058±0.105, 0.885±0.124, 0.972±0.136） was significantly higher than that of the group A （0.788±0.036, 0.585±0.017, 0.692±0.017, 0.527±0.051） （P=0.001, P=0.006, P=0.003, P=0.028） in each period, while group A was significantly higher than group B（0.247±0.022, 0.240±0.034, 0.134±0.011, 0.103±0.050） （P=0.000, P=0.001, P=0.002, P=0.012）.Conclusions PTH can upregulate the expression of osteoprotegerin and reduce expression of RANKL, thus promoting new bone formation. Intermittent administration of high dose of parathyroid hormone can further promote the healing process after mandibular ramus osteotomy.