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从标本兼治角度探讨补肾活血法调控OPG/RANKL/RANK/C-FOS与PPARγ/UCP1通路治疗绝经后骨质疏松的骨-脂代谢机制

批准号:
82060872
项目类别:
地区科学基金项目
资助金额:
34.0 万元
负责人:
安方玉
依托单位:
学科分类:
中医骨伤科学
结题年份:
2024
批准年份:
2020
项目状态:
已结题
项目参与者:
安方玉

项目摘要

结项摘要

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中文摘要
中医学认为绝经后骨质疏松属于本虚标实之证,肾虚为本,血瘀为标,治宜标本兼治,补肾活血。藤黄健骨胶囊作为补肾活血法的代表方药,前期研究证实其具有抗骨质疏松作用,网络药理学研究也表明,藤黄健骨胶囊中的关键成分山奈酚等可能通过OPG/RANKL/RANK(骨代谢)和PPAR(脂代谢)等途径发挥治疗作用,但骨-脂代谢的相互作用机制尚不清楚。基于此,我们提出以下假说:藤黄健骨胶囊可能通过抑制OPG/RANKL/RANK/C-FOS和PPARγ/UCP1通路,且两条信号通路交互作用调节骨-脂代谢,发挥治疗作用。本项目拟用藤黄健骨胶囊干预去卵巢骨质疏松大鼠模型,检测其疗效;运用HE、ELISA、免疫组化、RT-PCR和Western Blot等方法检测OPG/RANKL/RANK/C-FOS及PPARγ/UCP1信号通路中关键分子的表达,为藤黄健骨胶囊多环节、多靶点、综合调节绝经后骨质疏松提供依据。
英文摘要
Traditional Chinese medicine believes that the postmenopausal osteoporosis was a virtual real standard of evidence, in this virtual kidney, the deficiency is in blood stasis. The main treatment method was treating both specimens and invigorating the kidney and promoting blood circulation. Tenghuang jiangu capsule as the representative prescription of tonifying kidney and promoting blood circulation, the previous studies shows that it has been proved to be effective in treating osteoporosis, the network pharmacology research also indicated that the kaempferol component of tenghuang jiangu capsule may play a therapeutic role through OPG/ RANKL/RANK (bone metabolism) and PPAR (lipid metabolism), but the mechanism of bone lipid interaction is not clear. Based on this, we proposed the following hypothesis: tenghuang jiangu capsule may play a role by inhibiting OPG/RANKL/RANK/C-FOS and PPAR γ/UCP1 signaling pathway and affecting the interaction of two signaling pathways regulates bone lipid metabolism. In this project, tenghuang jiangu capsule is proposed to be used to intervene the ovariectomized rats and its curative effect was tested. The expression of key molecules in OPG/RANKL/RANK/C-FOS and PPARγ/UCP1 signaling pathway was used to detect by HE, ELISA, immunohistochemistry, RT-PCR and Western Blot. The aim was to provide evidence for the comprehensive regulation of postmenopausal osteoporosis from multiple links and multiple targets of tenghuang jiangu capsule.
绝经后骨质疏松症(PMOP)是一种以骨-脂代谢异常为特征的慢性骨病。然而,在PMOP的发生发展中,骨-脂质代谢之间的关系以及潜在机制尚不清楚。基于此,本课题以OPG/RANKL/RANK/C-FOS通路(骨代谢通路)和PPARγ/UCP1通路(脂代谢通路)为切入点,依据PMOP的主要病机肾虚血瘀,选用具有补肾活血功效的藤黄健骨胶囊(TJC)干预OVX模型大鼠,通过测定其股骨BMD、BMC,观察股骨病理形态、骨微结构及骨微结构参数变化,测定血清Ca2+、P含量变化,确定TJC对OVX模型大鼠的治疗作用;基于网络药理学技术筛选TJC治疗PMOP的关键靶点和通路;测定各组大鼠OCN、TRAP等骨代谢相关生化指标,E2、FSH、LH等内分泌激素指标及OPG/RANKL/RANK/C-FOS通路分子RANKL、RANK、C-FOS的表达,检测各组大鼠FFA、Apo A等脂代谢相关生化指标以及PPARγ/UCP1通路分子PPARγ、UCP1的表达,初步揭示TJC治疗PMOP的作用机制。结果提示:TJC通过升高OVX模型大鼠股骨BMD、BMC含量和血清Ca2+和P含量,同时升高其股骨BV/TV、Tb.N、Tb.Th和降低其股骨Tb.Th来改善其股骨形态结构损伤,从而发挥疗效。网络药理学结果证实TJC治疗PMOP的关键靶点是TAKT1、IL6、PPARG等,关键通路是类固醇激素生物合成通路等脂代谢相关通路。本研究实验结果也证实TJC可以通过激活OVX模型大鼠骨代谢OPG/RANKL/RANK/C-FOS通路和抑制脂代谢PPARγ/UCP1通路来促进成骨形成、抑制破骨分化和脂肪生成,从而发挥抗PMOP作用。本实验探明了PMOP的骨-脂代谢失衡机制及补肾活血法的干预效果,为合理筛选PMOP的新型中药制剂和中医药防治PMOP提供了科学依据。
从标本兼治角度探讨补肾活血法调控OPG/RANKL/RANK/C-FOS与PPARγ/UCP1通路治疗绝经后骨质疏松的骨-脂代谢机制
  • 批准号:
    --
  • 项目类别:
    --
  • 资助金额:
    34万元
  • 批准年份:
    2020
  • 负责人:
    安方玉
  • 依托单位:
国内基金
海外基金