文章摘要
张慧丽,李克峰,戴小丽,李仕红.基于兔骨质疏松模型的骨质疏松症进展中骨髓代谢组学变化[J].南京医科大学学报,2020,(11):1603~1611
基于兔骨质疏松模型的骨质疏松症进展中骨髓代谢组学变化
Metabolic changes in bone marrow during the progression of osteoporosis using a rabbit osteoporotic model
投稿时间:2019-08-07  
DOI:10.7655/NYDXBNS20201106
中文关键词: 磁共振波谱  骨髓  骨质疏松症  代谢组学分析  时间动态变化
英文关键词: proton magnetic resonance spectroscopy  bone marrow  osteoporosis  metabolomics analysis  temporal changes
基金项目:江苏省自然科学基金(BK20151293);“2017年江苏高校青蓝工程优秀青年骨干教师”培育项目
作者单位
张慧丽 江苏医药职业学院医学影像学院江苏 盐城 224005 
李克峰 美国加州大学圣地亚哥分校医学院美国 圣地亚哥 92103 
戴小丽 江苏医药职业学院临床医学院江苏 盐城 224005 
李仕红 江苏医药职业学院医学影像学院江苏 盐城 224005 
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中文摘要:
      目的:探讨兔骨质疏松症(osteoporosis,OP)发生过程中骨髓代谢的变化特点。方法:通过兔双侧卵巢切除术(ovariectomy,OVX)制作兔OP模型模拟绝经期妇女的OP过程。双能X线吸收测量法测量骨密度(bone mineraldensity,BMD)的变化。通过活体磁共振氢质子波谱(proton magnetic resonance spectroscopy,1H?MRS)和离体液相色谱结合质谱(LC?MS/MS)分析等多种方法对骨髓进行代谢组学分析。OVX组和假手术组(Sham组)的取样分析节点均分别设定在术前、术后2个月和术后5个月。结果:随着时间的发展,术后5个月OVX组的BMD值较Sham组明显减低(2个月,P<0.05;5个月,P<0.01)。1H?MRS扫描分析表明,与Sham组相比,OVX组骨髓中的乳酸和脂类含量在术后2个月和5个月时均明显增加。OVX组骨髓中的胆碱、肌酸、谷氨酰胺、羟脯氨酸却较Sham组减少。在术后2个月时,进行离体骨髓代谢组学分析,也得到了上述相似的骨髓代谢变化结果。此外,1H?MRS扫描分析发现,OVX组的氨基酸、酰基肉碱、核苷酸和神经酰胺发生了显著变化。相关分析发现,BMD值与乳酸值之间呈明显负相关(r=-0.842,P < 0.01),BMD与胆碱、肌酸、谷氨酰胺和羟脯氨酸呈显著正相关。结论:本研究发现随着OP进展,骨髓代谢会发生一系列复杂变化。利用1H?MRS对活体进行骨代谢变化扫描分析可能是评价OP的一种潜在无创方法。
英文摘要:
      Objective:This study aims to investigate the metabolic changes in bone marrow of female rabbits during the development of osteoporosis(OP). Methods:The rabbit osteoporotic model was created by ovariectomy(OVX). The loss of bone mineral density(BMD)was evaluated by dual?energy X?ray absorptiometer(DXA). Metabolomic profiling of bone marrow was conducted through a multiplatform approach including in vivo proton magnetic resonance spectroscopy(1H?MRS)and in vitro liquid chromatography coupled to mass spectrometry(LC?MS/MS)?based analysis. The analysis was conducted before the surgery(baseline),2?month and 5?month after the surgery. Results:BMD in OVX group decreased gradually over time and was significantly lower than the Sham group at 5?month after OVX(2?month,P < 0.05;5?month,P < 0.01). 1H?MRS analysis showed lactate and lipid in bone marrow were significantly increased in OVX group. Compared to Sham group,choline,creatine,glutamine and hydroxyproline in bone marrow of OVX qroup decreased dramatically. Similarly,in vitro metabolomic analysis of bone marrow showed dramatic metabolic changes as early as 2?month during the development of osteoporosis. In vivo 1H?MRS analysis showed that,compared to the Sham group,amino acids,acylcarnitines,nucleotides and ceramides were significantly altered. Correlation analysis identified a significant negative correlation between BMD and lactate(r=-0.842,P < 0.01). Significant positive correlations were found between BMD and choline,creatine,glutamine and hydroxyproline. Conclusion:Some complex and diverse changes in bone marrow metabolism was discovered in this study during the development of OP. In vivo analysis of bone metabolism using 1H?MRS might be a potential non?invasive approach for the evaluation of OP.
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