骨疏康治疗去卵巢大鼠骨质疏松的腰椎代谢组学分析

Anti-osteoporosis effect of Gushukang in ovariectomized rats:a lumbar metabonomic analysis

背景:骨疏康对骨质疏松症的具体分子作用机制和治疗靶点研究不足,需进一步研究探讨。目的:为进一步探索骨疏康治疗骨质疏松症的具体机制及作用靶点,利用超高效液相色谱-四级杆-飞行时间串联质谱技术的非靶向代谢组学方法,分析鉴定去卵巢大鼠腰椎的代谢物变化,探讨骨疏康对去卵巢大鼠骨质疏松症的治疗作用和潜在机制。方法:选择雌性SD大鼠,随机分为模型组、骨疏康组及假手术组,前两组采用去卵巢法建立骨质疏松症模型。造模4周后,骨疏康组大鼠给予骨疏康灌胃;假手术组和模型组分别给予等体积生理盐水灌胃。连续灌胃12周后利用超高效液相色谱-四级杆-飞行时间串联质谱技术进行大鼠腰椎代谢物分析,筛选出共同差异代谢物,对其进行京都基因与基因组百科全书通路等生物信息学分析。结果与结论:①3组共筛选出24种共同显著性差异代谢物;②京都基因与基因组百科全书富集分析表明,骨疏康可能调节脂肪酸代谢、甘油磷脂代谢、氨基酸代谢等重要通路参与保护骨质疏松模型大鼠的骨代谢过程;③结果显示,骨疏康可能通过干预脂质代谢和氨基酸代谢发挥其抗骨质疏松作用,从而达到预防骨质疏松症的目的。

BACKGROUND:The research on the specific molecular mechanisms and therapeutic targets of Gushukang on osteoporosis is insufficient,which needs further research and discussion.OBJECTIVE:To analyze and identify the changes of lumbar metabolites in ovariectomized rats,explore the therapeutic effect of Gushukang on osteoporosis in ovariectomized rats and discuss its potential mechanism by using the non-targeted metabonomics of ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass,thereby to further explore the specific mechanisms and targets of Gushukang in the treatment of osteoporosis.METHODS:Female Sprague-Dawley rats,which were ovariectomized to establish osteoporosis model,were divided into model group,Gushukang group,and sham operation group.Osteoporotic models were established using ovariectomy.Four weeks after modeling,rats in the Gushukang group were given Gushukang by gavage;and those in the sham operation and model groups were given the equal volume of normal saline.After 12 weeks of continuous gavage,the lumbar metabolites of rats were analyzed by the ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass technology,and the common differential metabolites were selected for bioinformatics analysis using Kyoto Encyclopedia of Genes and Genomes pathway.RESULTS AND CONCLUSION:A total of 24 common significant differential metabolites were identified in the three groups.Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that Gushukong could regulate important pathways such as fatty acid metabolis m,glycerol phospholipid metabolism and amino acid metabolism,and participate in the protection of bone metabolism in osteoporosis model rats.These findings indicate that Gushukong exerts its anti-osteoporosis effect by interfering with lipid metabolism and amino acid metabolism,so as to achieve the purpose of preventing osteopo rosis.