异紫杉脂素治疗对去卵巢大鼠骨量流失和骨密度降低保护作用的机制研究

Mechanism of protective effect of isotaxiresinol on bone mass loss and bone mineral density reduction in ovariectomized rats

目的探索异紫杉脂素(isotaxiresinol,IXO)对去卵巢大鼠骨密度和骨量的影响,并探讨其作用机制。方法将大鼠随机分为以下各组:假手术组(Sham)、去卵巢大鼠组(OVX)、去卵巢大鼠+异紫杉脂素组(IXO)。其中IXO组大鼠给予异紫杉脂素100 mg/(kg·d)治疗12周。Micro-CT和HE切片观察骨组织变化。通过ELISA检查用于分析骨代谢指标,进行蛋白质印迹分析以评估PI3K、Akt和RUNX-2的蛋白表达。结果12周时,OVX组大鼠骨密度和骨量较Sham组显著降低。而IXO能显著改善去卵巢大鼠的骨密度和股骨干骺端骨小梁微观结构。去卵巢大鼠在IXO给药治疗后可显著降低P1NP和β-CTX水平(P<0.05);用IXO治疗可上调去卵巢大鼠的PI3K、Akt和RUNX-2蛋白表达。结论本研究提示异紫杉脂素可以通过激活PI3K/Akt信号通路对去卵巢大鼠骨量流失和骨密度降低起到保护作用。

Objective To explore the effect of isotaxiresinol(IXO)on bone mineral density and bone mass in ovariectomized rats and to explore its mechanism of action.Methods The rats were randomly divided into the following groups:sham operation group(Sham),ovariectomized rats group(OVX),and ovariectomized+IXO group(IXO).In the IXO group,rats received 100 mg/kg/day of IXO for 12 weeks.Micro-CT and HE sections were used to observe bone tissue changes.Bone metabolism indicators were examined with ELISA.Western blotting analysis was performed to assess protein expressions of PI3K,Akt,and RUNX-2.ResultsAt 12 weeks,the bone mineral density and bone mass of rats in the OVX group were significantly lower than those in the Sham group.IXO significantly improved the bone mineral density and trabecular bone microstructure of the femoral metaphysis in ovariectomized rats.P1NP andβ-CTX levels were significantly reduced in ovariectomized rats after IXO administration(P<0.05).Treatment with IXO significantly up-regulated protein expressions of PI3K,Akt,and RUNX-2 in ovariectomized rats.ConclusionThis study suggests that IXO protects the bone loss and bone mineral density reduction in ovariectomized rats by activating the PI3K/Akt signaling pathway.