续苓健骨方对骨质疏松模型大鼠miRNA表达谱的作用研究

Study on the effect of Xuling-Jiangu Formula on miRNA expression profile in osteoporosis model rats

目的通过分析骨质疏松症大鼠模型miRNA表达谱变化,探讨续苓健骨方治疗骨质疏松症的分子机制。方法建立去卵巢法骨质疏松模型大鼠12只,分为模型组6只、续苓健骨方组6只。假手术组6只为对照。造模1个月后,续苓健骨方灌胃12周,检测大鼠胫骨骨密度,检测腰椎miRNA表达谱,对差异表达的miRNAs进行生物信息学分析。结果与假手术组比较,模型组腰椎miRNAs 58条显著下调、97条显著上调;与模型组比较,续苓健骨方组腰椎miRNAs下调的50条显著上调、上调的60条显著下调;与假手术组比较,续苓健骨方组腰椎miRNAs仅8条有差异。生物信息学分析发现,差异miRNAs靶基因主要参与HIF-1、甲状腺激素、Hedgehog、GnRH、自噬、cAMP及MAPK等信号通路。结论建立了续苓健骨方治疗骨质疏松模型大鼠的miRNA表达谱;差异miRNAs可能通过调控HIF-1、甲状腺激素、Hedgehog、GnRH、自噬、cAMP及MAPK等信号通路参与续苓健骨方对骨质疏松大鼠的治疗过程。

Objective To explore the molecular mechanism of Xuling-Jiangu Formula in the treatment of osteoporosis by analyzing the changes of miRNA expression profile in rat model of osteoporosis.Methods Twelve rats of osteoporosis model were established by ovarian removal method,of which 6 were in the model group,6 were in the Xuling-Jiangu Formula group.Six rats in the sham operation group were as controls.One month after modeling,rats were administrated by gavage with Xuling-Jiangu Formula for 12 weeks.BMD of the tibia was measured.The expression profile of lumbar miRNA in different groups was detected.Bioinformatics analysis was performed for the differentiated expression of miRNAs.Results Compared with those in the sham operation group,58 lumbar miRNAs were significantly down-regulated and 97 were significantly up-regulated in the model group.Compared with those in the model group,50 down-regulated lumbar miRNAs were significantly up-regulated and 60 up-regulated ones were significantly down-regulated in the Xuling-Jiangu Formula group;Compared with those in the sham operation group,only 8 lumbar miRNAs were different in the Xuling-Jiangu Formula group.Bioinformatics analysis revealed that differential miRNA target genes were mainly involved in signaling pathways such as Hif-1,thyroid hormone,Hedgehog,GnRH,autophagy,CAMP,and MAPK.Conclusion The miRNAs expression profile of Xuling-Jiangu Formula in the treatment of osteoporosis model rats was established;Differential miRNAs may be involved in the treatment of osteoporosis rats by regulating Hif-1,thyroid hormone,Hedgehog,GnRH,autophagy,CAMP,MAPK,and other signaling pathways.