Mei Runhong, Chen Dan, Zhong Duming, Li Guoyong, Lin Shaobai, Zhang Guangquan, Chen Kaiyun, Yu Xuefeng
Department of Orthopaedics, The Fourth Affiliated Hospital of Nanchang University, Nanchang, China.
Department of Drug Clinical Trial, The Fourth Affiliated Hospital of Nanchang University, Nanchang, China.
Front Pharmacol. 2022 May 2;13:845856. doi: 10.3389/fphar.2022.845856. eCollection 2022.
Gushiling capsule (GSLC) is an effective traditional Chinese medicine for the treatment of glucocorticoid-induced osteonecrosis of the femoral head (GIONFH). This study established the serum metabolite profiles of GSLC in rabbits and explored the metabolic mechanism and effect of GSLC on GIONFH. Seventy-five Japanese white rabbits were randomly divided into the control, model, and GSLC groups. The rabbits in the model group and the GSLC group received injection of prednisolone acetate. Meanwhile, rabbits in the GSLC group were treated by gavage at a therapeutic dose of GSLC once a day. The control group and the model group received the same volume of normal saline gavage. Three groups of serum samples were collected at different time points, and the changes in the metabolic spectrum were analyzed by ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The resulting data set was analyzed using multivariate statistical analysis to identify potential biomarkers related to GSLC treatment. The metabolic pathway was analyzed by MetaboAnalyst 4.0 and a heatmap was constructed using the HEML1.0.3.7 software package. In addition, histopathological and radiography studies were carried out to verify the anti-GIONFH effects of GSLC. Principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) score plots revealed a significant separation trend between the control group and the model group and the GSLC group (1-3 weeks), but there were no significant differences in the GSLC group (4-6 weeks). Orthogonal PLS-DA (OPLS-DA) score plots also revealed an obvious difference between the model and the GSLC groups (4-6 weeks). Ten potential metabolite biomarkers, mainly phospholipids, were identified in rabbit serum samples and demonstrated to be associated with GIONFH. Hematoxylin and eosin staining and magnetic resonance imaging indicated that the pathological changes in femoral head necrosis in the GSLC group were less than in the model group, which was consistent with the improved serum metabolite spectrum. GSLC regulated the metabolic disorder of endogenous lipid components in GIONFH rabbits. GSLC may prevent and treat GIONFH mainly by regulating phospholipid metabolism .
骨蚀灵胶囊（GSLC）是治疗糖皮质激素性股骨头坏死（GIONFH）的一种有效中药。本研究建立了兔体内GSLC的血清代谢物谱，并探讨了GSLC对GIONFH的代谢机制及作用。75只日本大白兔随机分为对照组、模型组和GSLC组。模型组和GSLC组的兔子接受醋酸泼尼松龙注射。同时，GSLC组的兔子以GSLC治疗剂量每日一次灌胃给药。对照组和模型组接受相同体积的生理盐水灌胃。在不同时间点采集三组血清样本，采用超高效液相色谱-串联质谱（UPLC-MS/MS）分析代谢谱的变化。使用多元统计分析对所得数据集进行分析，以鉴定与GSLC治疗相关的潜在生物标志物。通过MetaboAnalyst 4.0分析代谢途径，并使用HEML1.0.3.7软件包构建热图。此外，进行组织病理学和影像学研究以验证GSLC对GIONFH的防治作用。主成分分析（PCA）和偏最小二乘判别分析（PLS-DA）得分图显示对照组与模型组和GSLC组（1 - 3周）之间有明显分离趋势，但GSLC组（4 - 6周）无显著差异。正交PLS-DA（OPLS-DA）得分图也显示模型组与GSLC组（4 - 6周）之间存在明显差异。在兔血清样本中鉴定出10种潜在的代谢物生物标志物，主要为磷脂，并证明与GIONFH相关。苏木精-伊红染色和磁共振成像表明，GSLC组股骨头坏死的病理变化小于模型组，这与血清代谢物谱的改善一致。GSLC调节GIONFH兔体内内源性脂质成分的代谢紊乱。GSLC可能主要通过调节磷脂代谢来防治GIONFH。
Zotero 插件
