基于GC-MS的骨疏丹预防糖皮质激素性骨质疏松代谢组学研究  

Metabolomics analysis for the intervention effects of Gushudan on glucocorticoid-induced osteoporotic rat based on GC-MS

作　　者：袁雪梅 孙毅[2] 贾惠雯 刘硕[1] 赵晶 熊志立[1] YUAN Xuemei;SUN Yi;JIA Huiwen;LIU Shuo;ZHAO Jing;XIONG Zhili(School of Pharmacy,Shenyang Pharmaceutical University,Shenyang 110016,China;Beijing Institute For Drug Control,Beijing 102206,China)

机构地区：[1]沈阳药科大学药学院,辽宁沈阳110016 [2]北京市药品检验所,北京102206

出　　处：《沈阳药科大学学报》2021年第10期1033-1039,共7页Journal of Shenyang Pharmaceutical University

基　　金：国家自然科学基金资助项目(81773694)。

摘　　要：目的建立基于GC-MS的代谢组学方法,考察糖皮质激素性骨质疏松(glucocorticoid-induced osteoporosis,GIOP)大鼠尿液内源性代谢物的变化,寻找与骨质疏松相关的潜在生物标志物,探讨骨疏丹(Gushudan,GSD)干预GIOP大鼠尿液代谢物的变化及其预防骨质疏松的作用机制。方法建立正常对照组、GIOP模型组和GSD给药组大鼠尿液的GC-MS代谢指纹图谱,利用偏最小二乘判别分析(PLS-DA)研究给药前后大鼠尿液中内源性代谢物变化,寻找潜在生物标志物,探讨GSD的作用机制。结果经PLS-DA模式识别分析,对照组、模型组和GSD给药组能够得到很好的区分,共发现了牛磺酸、丙二酸等11种潜在生物标志物,苹果酸、L-苏糖酸等是新发现的与骨质疏松症相关的潜在生物标志物。这些潜在生物标志物主要与氨基酸代谢、能量代谢、脂肪酸代谢和体内的氧化应激状态相关,GSD给药后骨质疏松模型大鼠的内源性代谢物水平发生不同程度的回调。结论基于GC-MS的代谢组学方法可以很好的从内源性代谢物的变化过程反应GIOP的发生情况,同时也表明代谢组学在中药整体药效评价、作用机制研究等方面具有很好的应用前景。Objective To develop an integrated urinary metabonomic strategy based on gas-chromatography-mass spectrometry(GC-MS)method,to search for potential biomarkers and to discuss the anti-osteoporosis mechanism of Gushudan(GSD).Methods The rats were divided into the control group,GIOP model group and GSD administration group.The GC-MS technique was used to detect the metabolite spectra in rats urine.The data were analyzed by partial least squares-discriminant analysis(PLS-DA)to study the changes of endogenous metabolites before and after administration,to search for potential biomarkers,and to explore the possible mechanism of GSD.Results PLS-DA showed that there was significantly different of metabolic profiling between control group,model group and GSD administration group.A total of 11 differential metabolites were identified,which were mainly related to amino acid metabolism,energy metabolism and oxidative stress.GSD had significant anti-osteoporotic effects on glucocorticoid-induced osteoporosis in rat plasma,which might be attributed to the regulation of multiple metabolic pathways.It's worth mentioning that some new potential biomarkers,associated with osteoporosis such as malic acid and L-threonic acid,were discovered for the first time.Conclusion Metabonomic study based on GC-MS shows a good recognition of glucocorticoid osteoporosis rats,which will provide reference for early diagnosis of osteoporosis.

关 键 词：气相色谱质谱联用法 骨疏丹 尿液 代谢组学 

分 类 号：R917[医药卫生—药物分析学]