雌性激素对骺生长板闭合过程的影响

Effect of estrogen on epiphyseal growth plate fusion

目的:了解雌性激素对骺生长板闭合过程的影响。方法:实验于2003-07/2004-03在重庆医科大学动物实验中心完成。选用性发育前(12周龄)的新西兰雌兔40只,切除双侧卵巢后随机分为雌二醇组和对照组各20只,4周后(16周龄)雌二醇组肌肉注射雌二醇(140 μg/kg,1次/周),对照组肌肉注射等体积不含雌二醇的灭菌棉籽油。从16周龄开始2组中各抽取5只动物,每两周1次进行跟踪股骨X射线拍片,直至29周龄,测定股骨生长率。血清雌二醇测定采用ELISA法。两组分别于20,23,26周龄时各处死5只,取股骨远端、胫骨近端和胫骨远端骺生长板作组织病理学分析及组织计量学测定,了解雌性激素对骺生长板生理性闭合时间、骺生长板组织形态结构和软骨细胞增殖率的影响。结果:雌兔40只全部进入结果分析。①血清雌二醇水平:干预前2组比较差异不显著,肌肉注射雌二醇后各时期雌二醇组均高于对照组(P<0.05)。②股骨生长率:两组均随年龄增长逐渐降低,至性成熟后(28周龄)股骨生长基本趋于停止。雌二醇组性发育早期(18周龄)快于对照组[(2.5±0.20),(2.2±0.05)mm/周,P<0.05],但20周龄后增长逐渐减慢,低于对照组。③骺生长板闭合时间:两组动物在20周时胫骨远端生长板均已发生闭合,雌二醇组胫骨近端和股骨远端生长板在23～26周龄闭合,而对照组闭合的时间延长或实验结束时仍未发生闭合。④骺生长板组织形态结构:雌二醇组雌兔骺生长板厚度和细胞柱密度显著低于对照组(P<0.05),对照组骺生长板出现“病理性”增厚。⑤生长板软骨细胞增殖率:雌二醇组股骨远端和胫骨近端生长板软骨细胞增殖率在20和23周龄均高于对照组(P<0.05),26周龄时,雌二醇组大部分雌兔骺生长板已经闭合,对照组仍可检出。结论:雌性激素早期可促进骺生长板软骨细胞增殖,提高长骨生长率,作用中、后期引起骺生长板组织结构发生衰退性改变促进骺生长板生理性闭合过程。

AIM： To explore the effects of estrogen on the epiphyseal growth plate fusion. METHODS： The experiment was conducted in the animal experimental center of Chongqing University of Medical Sciences between July 2003 and March 2004. Forty New Zealand rabbits pre-sexual development （12 weeks old） were selected and randomly divided into estradiol group and control group with 20 rabbits in each group after ovariectomy. Four weeks later （16 weeks old）, the rabbits in the estradiol group were given intramuscular injection of estradiol （140 μg/kg, once per week）; the control group was injected matching sterile cotton oil without estradiol. Since 16-week-old, the tracking gradiograph was performed every 2 weeks until 29 weeks old to measure the femoral growth rata among the 5 animals selected respectively from the two groups. The estradiol levels of the plasma were detected with ELISA method. Five rabbits in each group were skilled at 20, 23 and 26 weeks old respectively to remove the distal femur, proximal tibia and distal tibia epiphyseal growth plate for quantitative histology evaluations, so as to explore the effects of estrogen on the time of growth plate fusion, tissue structure of epiphyseal growth plate and proliferative rate of chondrocyte. RESULTS：All 40 female rabbits were involved in the result analysis. ①Estradiol levels： No significant difference was found in the two groups before intervention. After injection of estradiol, the levels of the estradiol group were higher than the control group at each stage （P 〈 0.05）.②Growth rates of femur： The growth rates of the two groups were decreased with age, and stopped growing at 28 weeks old. The growth condition of the estradiol group was faster than the control group at early sexual development （18 weeks old） [（2.5±0.20）, （2.2±0.05） mm per week, P 〈 0.05], but began to slow since 20 weeks old and lower than the control group. ③Time for growth plate fusion： At 20 weeks, the distal tibia growth plate of the two groups had fused; the proximal tibia and distal femur of the estradiol group fused at 23 to 26 weeks old, but the control group did not fused. ④Structure of epiphyseai growth plate： The thickness of the plate and the density of cell pillar of the estradiol group were obviously lower than the control group （P 〈 0.05）, and the growth plate of the control group appeared ＂pathological＂ thickening. ⑤Proliferative rates of chondrocyte： The proliferative rates of distal femur and proximal tibia of the estradiol group at 20 and 23 weeks old were higher than the control group （P 〈 0.05）. At 26 weeks old, most of the epiphyseal growth plate of the estradiol group had fused, but the control group was not. CONCLUSION： Estrogen at early stage can promote the chondrocyte proliferation and increase the growth rate of bone; at middle or later stage can induce structure senescence and accelerate the process of growth plate fusion.