酒精性和激素性股骨头坏死的外周血脂质组学分析  

Lipid metabolism analysis for peripheral blood in patients with alcohol-induced and steroid-induced osteonecrosis of the femoral head

作　　者：闫玉珠 于燕[1] 刘俊叶 赵和平[1] 王冀邯 YAN Yuzhu;YU Yan;LIU Junye;ZHAO Heping;WANG Jihan(Department of Clinical Laboratory,Honghui Hospital,Xi’an Jiaotong University,Xi’an 710054;Xi’an Key Laboratory of Stem Cell and Regenerative Medicine,Institute of Medical Research,Northwestern Polytechnical University,Xi’an 710072,China)

机构地区：[1]西安交通大学附属红会医院检验科,西安710054 [2]西北工业大学医学研究院西安市干细胞与再生医学重点实验室,西安710072

出　　处：《中南大学学报（医学版）》2022年第7期872-880,共9页Journal of Central South University ：Medical Science

基　　金：陕西省自然科学基金(2020JM-691);西安市科技计划项目[2019115013YX005SF038(10)]。

摘　　要：目的:股骨头坏死(osteonecrosis of the femoral head,ONFH)又被称为股骨头缺血性坏死,多数患者并发脂肪代谢紊乱。本研究探讨不同亚型的ONFH的脂代谢表达谱模式。方法:将受试者分为酒精性股骨头坏死(alcohol-induced osteonecrosis of the femoral head,AONFH)组(n=16)、激素性股骨头坏死(steroid-induced osteonecrosis of the femoral head,SONFH)组(n=29)、正常对照(normal control,NC)组(n=32)。运用超高效液相色谱-质谱/质谱串联(ultra high performance liquid chromatography-mass spectrometry/mass spectrometry tandem apparatus,UPLC-MS/MS)技术对受试者的外周血标本进行脂质代谢物的检测,鉴定疾病潜在的生物标志物。对代谢物表达谱进行预处理,再通过偏最小二乘法判别分析(partial least squares discriminant analysis,PLS-DA)计算变量投影重要度(variable importance for the projection,VIP)来衡量各脂质代谢物的表达模式对各组样本分类判别的影响强度和解释能力。筛选出不同组间倍数改变(fold change,FC)>2、P<0.05且VIP>1的脂质代谢物作为差异脂质物。其中,AONFH组和SONFH组中共同存在的差异脂质物被视为ONFH的共有差异脂质物,单独存在的差异脂质物被视为AONFH组或SONFH组的特异性差异脂质物。在差异脂质物的受试者操作特征(receiver operator characteristic,ROC)曲线分析的基础上,采用二元logistic回归评价差异脂质物对疾病的诊断价值。依据AONFH组和SONFH组患者的疾病分期信息,分析差异脂质物与疾病分期之间的相关性。结果:在血浆样本中共检测到1358种脂质代谢物。与NC组相比,AONFH组和SONFH组脂质代谢谱表达模式均有显著差异。分别在AONFH组和SONFH组患者外周血中筛选出62和64种差异脂质物(FC>2,P<0.05,VIP>1),且均以上调为主。进一步鉴定出AONFH组和SONFH组共有的差异脂质物有9种,AONFH组有6种脂质物的ROC曲线下面积大于0.7,它们分别为1-myristoyl-2-docosahexaenoyl-sn-glycObjective:Osteonecrosis of the femoral head(ONFH),also known as vascular necrosis of the femoral head,is combined with lipid metabolism disorders in most patients.This study aims to explore the lipid metabolism profiles in different subtypes of ONFH.Methods:The subjects were divided into an alcohol-induced osteonecrosis of the femoral head(AONFH)group,a steroid-induced osteonecrosis of the femoral head(SONFH)group,and a normal control(NC)group(n=16,29,and 32,respectively).Ultraperformance liquid chromatography-mass spectrometry/mass spectrometry(UPLC-MS/MS)was used to detect the lipidomics analysis in the peripheral blood samples of subjects and identify the underlying biomarkers.The samples were preprocessed,the partial least squares discriminant analysis(PLS-DA)was adopted,and the variable importance for the projection(VIP)values were calculated to measure the expression pattern of each lipid metabolite and observe the influence and explanatory power of the expression pattern of each lipid metabolite on the classification and discrimination between the different groups.The lipid metabolites with fold change(FC)>2,P<0.05 and VIP>1 in the different groups were screened as differential lipids.Among them,the differential lipids co-existing in the AONFH group and the SONFH group were regarded as common differential lipids for ONFH,and the differential lipids that exist separately were regarded as specific differential lipids in the AONFH group or the SONFH group.Binary logistic regression was used to evaluate the diagnostic value of differential lipid metabolites on the basis of the receiver operator characteristic(ROC)curve analysis.Based on the disease stage information,the correlation between the differential lipids and the disease stage was analyzed in the AONFH group and the SONFH group.Results:In this study,1358 lipid metabolites were detected in each plasma sample.Compared with the NC group,there were significant difference in the expression patterns of lipid metabolism profiles in the AONFH group and the SON

关 键 词：酒精性股骨头坏死 激素性股骨头坏死 脂质组学 ARCO分期 生物标志物 

分 类 号：R681.8[医药卫生—骨科学]