去卵巢大鼠不同时期骨量、骨转换指标、雌激素水平的变化规律及相关性

Change rules and correlation between bone mass, bone turnover markers and estrogen levels in different periods of ovariectomized rats

背景:目前对去卵巢大鼠的研究较多,而对不同时间点大鼠骨量、骨转换指标、雌激素水平的变化规律及各因素的相关性研究报道较少。目的:分析去卵巢大鼠不同时期骨量、骨转换指标、雌激素水平的变化规律并探讨其相关性。方法:34只3月龄雌性SD大鼠,随机分为基线组、假手术组和去卵巢组。实验开始先将基线组处死,假手术组及去卵巢组于术后第4,8,12周分次处死。双能X射线吸收法(DXA)测定L1-3及股骨不同分区(头颈部R1区、转子部R2区、股骨干R3区、股骨整体R4区)的骨矿含量、骨密度、骨面积;酶联免疫吸附法(ELISA)检测血清Ⅰ型前胶原氨基端原肽、Ⅰ型胶原羧基端肽及雌激素水平。对大鼠体质量、离体骨密度、Ⅰ型前胶原氨基端原肽、Ⅰ型胶原羧基端肽、雌激素水平、月龄间的相关性进行分析。结果与结论:1去卵巢后4周去卵巢组离体腰椎及股骨骨矿含量、骨密度均较基线组、假手术组明显降低(P<0.05),第8,12周时均显著改善(P<0.05),腰椎、股骨各区域骨量丢失幅度最大的为L1及股骨转子区。2去卵巢后4周去卵巢组血清Ⅰ型前胶原氨基端原肽、Ⅰ型胶原羧基端肽水平较基线组、假手术组均显著升高(P<0.05),第8,12周差异无显著性意义。3去卵巢组第8,12周血清雌激素较假手术组及基线组明显降低(P<0.01,P<0.05)。4月龄与大鼠体质量、腰椎及股骨骨密度呈正相关,Ⅰ型前胶原氨基端原肽、Ⅰ型胶原羧基端肽与腰椎及股骨骨密度呈负相关(P<0.01)。提示去卵巢后大鼠腰椎、股骨骨量变化呈先快速降低、再缓慢回升的趋势,其中L1及股骨转子部受影响最大;骨转换指标在去卵巢后显著加快、后期逐渐回归正常;雌激素水平变化规律为第1个月先升高、后期快速降低;体质量、骨转换指标及雌激素水平与骨量密切相关。

BACKGROUND：There are so many studies about ovariectomized rats at present, but the research on the change rules of bone mass, bone turnover markers, estrogen levels and their correlation in different periods of ovariectomized rats is rarely reported. OBJECTIVE：To analyze the change rules of bone mass, bone turnover markers, estrogen level and their correlation in different periods of ovariectomized rats. METHODS： Thirty-four 3-month-old female Sprague Dawley rats were randomly divided into three groups： baseline group, ovariectomized group and sham operated group. At the beginning of the experiment, the rats in the baseline group were sacrificed, then rats in the ovariectomized group and sham operated group were executed at 4, 8, 12 weeks postoperative respectively. The bone mineral density, bone mass content, area of different zones of the L1-3 lumbar vertebrae and femurs were detected by dual-energy X-ray absorption method, and meanwhile the serum levels of type I procolagen amino-terminal pro-peptide, I colagen carboxy-terminal peptide and estrogen were determined by ELISA. At last, we analyzed the correlation between body mass, bone mineral densityin vitro, type I procolagen amino-terminal pro-peptide, I colagen carboxy-terminal peptide and estrogen levels and the age of ovariectomized rats. RESULTS AND CONCLUSION： （1） The bone mineral density and bone mass content of the lumbar vertebral and femurs in the ovariectomized group were significantly lower than those in the sham operated group and baseline group at the 4th week after operation （P 〈 0.05）. The bone mineral density and bone mass content in the ovariectomized group were ameliorated obviously at the 8th and 12th weeks compared with those at the 4th week after operation （P 〈 0.05）. The bone mass loss was highest in the L1 and intertrochanteric regions. （2） Serum levels of type I procolagen amino-terminal pro-peptide and I colagen carboxy-terminal peptide in the ovariectomized group were significantly higher than those in the baseline group and sham operated group at the 4th week after operation, but there was no difference at the 8th and 12th weeks. （3） The serum estrogen level in the ovariectomized group was prominently lower than that in the sham operated group and baseline group at the 8th and 12th weeks after operation （P 〈 0.01 at the 8th week,P 〈 0.05 at the 12th week）. （4） The age was positively correlated with body mass and bone mineral density of the lumbar vertebrae and femursin vitro, while the serum levels of type I procolagen amino-terminal pro-peptide and I colagen carboxy-terminal peptide were negatively correlated with the bone mineral density of the lumbar vertebrae and femurs in vitro （P 〈 0.01）. These results suggested that the bone mass of the lumbar vertebrae and femurs in ovariectomized rats was decreased rapidly firstly, and then rose slowly with time; the bone mass in the L1 and intertrochanteric regions lost seriously; the bone turnover markers showed a significant increase at the beginning of ovariectomy and reduced gradualy to normal condition, while the estrogen level was increased at the first month after ovariectomy and then decreased rapidly. In addition, the body mass, bone turnover markers and estrogen level were associated with the change of bone mass.