SLE合并SONFH患者血清差异表达蛋白筛查

Screening out the serum differentially expressed proteins in patients with SLE combined with SONFH

目的探讨系统性红斑狼疮(SLE)合并激素性股骨头坏死(SONFH)患者血清蛋白质组学表达差异,寻找并鉴定诊断SONFH的潜在生物学标志物。方法分别采集10例SLE合并SONFH患者(SONFH组)、5例健康者(对照组)的外周血,提取血清,去除高丰度血清蛋白质,采用同位素相对标记与绝对定量技术联合二维液相色谱-串联质谱技术进行蛋白组学分析,并进一步行GO和KEGG通路生物信息学分析,寻找并鉴定差异表达的蛋白质。结果与对照组比较,SONFH组共鉴定出16个差异表达蛋白,其中铜蓝蛋白、结合珠蛋白、IGHG1蛋白、免疫球蛋白重链1、C反应蛋白、补体C9、α1-酸性糖蛋白表达上调(P均<0.05),SERPINA4蛋白、凝溶胶蛋白、凝血因子Ⅻ、色素上皮细胞衍生因子、备解素、巯基氧化酶1、凝血因子ⅩⅢ、KRTDAP蛋白、胰岛素样生长因子结合蛋白3表达下调(P均<0.05)。KEGG通路分析提示以上16个蛋白与补体及凝血级联反应、系统性红斑狼疮、肌动蛋白细胞骨架调节、p53信号通路、卟啉和叶绿素代谢、FcγR-介导吞噬信号通路密切相关。结论成功从SLE合并SONFH患者血清筛选出差异表达蛋白,此16个蛋白可能是诊断SONFH的潜在生物学标志物。

Objective To investigate the differences in the serum proteomics in patients with systemic lupus erythematosus（ SLE） and steroid-induced osteonecrosis of the femoral head（ SONFH） and to find and identify the potential biomarkers of SONFH. Methods Peripheral blood was collected from 10 SLE patients with SONFH（ SONFH group） and 5 healthy controls（ control group）,respectively. Serum was extracted and the high abundance serum proteins were removed.The isotope relative labeling and absolute quantification combined with two-dimensional liquid chromatography-tandem mass spectrometry were used for the proteomics analysis,and then the GO and KEGG pathway bioinformatics analysis were used to find and identify the differentially expressed proteins. Results Compared with the control group,16 differentially expressed proteins were identified in the SONFH group,during which,the expression levels of ceruloplasmin,haptoglobin,IGHG1,immunoglobulin heavy chain 1,C-reactive protein,complement C9,and α1-acid glycoprotein were up-regulated（ all P 0. 05）,and the expression levels of SERPINA4,gelsolin,coagulation factor Ⅻ,pigment epithelial cells derived factor,properdin,thrombin oxidase 1,coagulation factor ⅩⅢ,KRTDAP,and insulin-like growth factor binding protein 3 were down-regulated（ all P 0. 05）. KEGG pathway analysis suggested that the above 16 proteins were closely related to complement and coagulation cascade,SLE,actin cytoskeleton regulation,p53 signaling pathway,porphyrin and chlorophyll metabolism,and FcγR-mediated phagocytosis signaling pathway. Conclusion Sixteen serum differentially expressed proteins from patients with SLE combined with SONFH are successfully screened out,and these 16 proteins may be the potential biomarkers of SONFH.