绝经后骨质疏松患者骨代谢与脂代谢的关系及血清蛋白质组学研究  

Serum proteomics study on the relationship between bone metabolism and lipid metabolism in postmenopausal osteoporosis

作　　者：林建立 林移婷 陈耀琦 胡张洁 蔡敏 LIN Jianli;LIN Yiting;CHEN Yaoqi;HU Zhangjie;CAI Min(Department of Endocrinology,Fujian Provincial Hospital Affiliatedto Fuzhou University,Fuzhou,Fujian 350001,China;Department of Endocrinology,Fuzhou Second General Hospital,Fuzhou,Fujian 350001,China;Department of Nuclear Medicine,Fujian Provincial Hospital Affiliated to Fuzhou University,Fuzhou,Fujian 350001,China;Department of Special Outpatient Services for Cadres,Fujian Provincial Hospital Affiliated to Fuzhou University,Fuzhou,Fujian 350001,China)

机构地区：[1]福州大学附属省立医院内分泌科,福州350001 [2]福建省福州市第二总医院内分泌科,福州350001 [3]福州大学附属省立医院核医学科,福州350001 [4]福州大学附属省立医院干部特诊二科,福州350001

出　　处：《福建医药杂志》2025年第2期1-4,F0002,共5页Fujian Medical Journal

基　　金：福建省自然科学基金项目(2016J01434)。

摘　　要：目的探讨绝经后骨质疏松(PMOP)患者脂代谢与骨代谢的关系,并通过血清蛋白质组学分析筛选相关标志物,为PMOP的诊断和治疗提供新思路。方法收集125例绝经后患者资料,按骨密度分为骨质疏松组(75例)和非骨质疏松组(50例)。采集两组各5例患者的血清进行定量蛋白质组学分析。通过质谱和生物信息学分析,筛选差异表达蛋白,并进行GO富集分析和PPI蛋白互作网络分析。结果骨质疏松组的甘油三酯(TG)、低密度脂蛋白(LDL)水平和颈动脉硬化斑块数量高于非骨质疏松组,差异有统计学意义(P<0.05)。Pearson相关性分析显示,腰椎、股骨颈和髋部骨密度(BMD)与TG、LDL和β-Ⅰ型胶原交联C末端肽(β-CTX)呈负相关(P<0.05),颈动脉硬化斑块数量越多,BMD越低(P<0.05)。蛋白质组学分析筛选出30个差异表达蛋白,其中脂联素和磷酸烯醇式丙酮酸羧激酶在骨质疏松组中表达上调。GO富集分析显示,差异蛋白主要富集在细胞过程、抗氧化活动、生物调节和信号传导等。PPI网络分析筛选出4个Hub基因:ADIPOQ、PCK2、CA3和CLIC1。结论骨质疏松组的TG、LDL和颈动脉硬化斑块数量升高,TG、LDL与BMD呈负相关。差异蛋白Q15848和Q16882可能通过腺苷单磷酸激活蛋白激酶(AMPK)信号通路影响骨代谢和脂质代谢,该发现为PMOP的诊断和治疗提供了潜在生物标志物。未来研究将进一步探讨其具体机制,为临床干预提供新靶点。Objective To investigate the relationship between lipid metabolism and bone metabolism in postmenopausal osteoporosis(PMOP)patients and to identify related biomarkers through serum proteomics analysis,providing new insights for the diagnosis and treatment of PMOP.Methods A total of 125 postmenopausal patients were collected and divided into osteoporosis group(75 cases)and non-osteoporosis group(50 cases)based on bone density.Serum samples from five randomly selected patients in each group were analyzed using quantitative proteomics.Differentially expressed proteins were identified through mass spectrometry and bioinformatics analysis,followed by GO enrichment analysis and PPI network analysis.Results Compared with the non-osteoporosis group,the levels of triglycerides(TG),low-density lipoprotein(LDL),and carotid atherosclerotic plaque count were significantly higher in the osteoporosis group(P<0.05).Pearson correlation analysis showed that bone mineral density(BMD)of the lumbar spine,femoral neck,and hip was negatively correlated with TG,LDL,andβ-C-terminal telopeptide of typeⅠcollagen(β-CTX)(P<0.05).Proteomics analysis identified 30 differentially expressed proteins,among which adiponectin and phosphoenolpyruvate carboxykinase were upregulated in the osteoporosis group.GO enrichment analysis indicated that these proteins were mainly involved in cellular processes,antioxidant activity,biological regulation,and signal transduction.PPI network analysis identified four hub genes:ADIPOQ,PCK2,CA3 and CLIC1.Conclusion The levels of TG,LDL,and carotid atherosclerotic plaque count are elevated in the osteoporosis group and negatively correlated with BMD.Differential proteins Q15848 and Q16882 may affect bone and lipid metabolism through the Adenosine Monophosphate Activated Protein Kinase(AMPK)signaling pathway,providing potential biomarkers for the diagnosis and treatment of PMOP.Future studies will further explore the specific mechanisms of these proteins to identify new therapeutic targets for clinical interventio

关 键 词：绝经后骨质疏松症 骨代谢 脂代谢 血清蛋白质组学 

分 类 号：R58[医药卫生—内分泌]