Ren Xiangnan, Fan Wu, Shao Zixing, Chen Kaiyun, Yu Xuefeng, Liang Qionglin
Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, China.
The Fourth Affiliated Hospital, Nanchang University, Nanchang 330003, China.
Oncotarget. 2018 Jan 10;9(8):7984-7995. doi: 10.18632/oncotarget.24150. eCollection 2018 Jan 30.
The early and accurate diagnosis of steroid-induced avascular necrosis of the femoral head (SANFH) is appealing considering its irreversible progression and serious consequence for the patients. The purpose of this study was to investigate the metabolic change of SANFH for its early detection. Two stages were designed in this study, namely discovery and verification. Except the biochemical index anomaly and the accidental death, 30 adult healthy adult Japanese white rabbits were used for screening out the potential metabolites in discovery experiment and 13 rabbits were used in verification experiment. The femoral heads were assessed with magnetic resonance imaging and transmission electron microscopy. The metabolomic profiling of serum samples were analysis by UHPLC-MS/MS. Metabolomic cluster analysis enable us to differentiate the rabbits without and with injection of the glucocorticoid in 1 week even when there is no obvious abnormal symptom in behaviors or imaging diagnosis. The majority of differential metabolites were identified as phospholipids which were observed significant change after injection of glucocorticoid in 1, 2, 3 weeks. And the results obtained in verification experiment of 6 weeks showed that these differential metabolites exhibited consistent trends in late progression with that in early-stage. At the end of 6 weeks the damage of SANFH could be verified by pathological imaging. Therefore the finding of serum metabolite profile links to the progression of SANFH and provides the potential of early detection of SANFH.
考虑到类固醇诱导的股骨头缺血性坏死（SANFH）不可逆转的进展及其对患者造成的严重后果，其早期准确诊断具有重要意义。本研究旨在通过探究SANFH的代谢变化以实现早期检测。本研究设计了两个阶段，即发现阶段和验证阶段。除生化指标异常和意外死亡外，30只成年健康日本白兔用于发现实验以筛选潜在代谢物，13只兔子用于验证实验。通过磁共振成像和透射电子显微镜对股骨头进行评估。血清样本的代谢组学分析采用超高效液相色谱-串联质谱法（UHPLC-MS/MS）。代谢组聚类分析使我们能够区分在注射糖皮质激素1周后未注射和已注射的兔子，即使在行为或影像学诊断中没有明显异常症状。大多数差异代谢物被鉴定为磷脂，在注射糖皮质激素1、2、3周后观察到其有显著变化。6周验证实验的结果表明，这些差异代谢物在疾病进展后期与早期呈现出一致的趋势。在6周结束时，可通过病理成像验证SANFH的损伤。因此，血清代谢物谱的发现与SANFH的进展相关，并为SANFH的早期检测提供了可能。
