实用医学杂志2025,Vol.41Issue(4):500-508,9.DOI:10.3969/j.issn.1006-5725.2025.04.006
基于Wnt/β-catenin信号通路介导的自噬和凋亡探讨苦豆子碱对骨质疏松小鼠骨代谢的影响
To investigate the effect of aloperine on bone metabolism in osteoporotic mice based on autophagy and apop-tosis mediated by Wnt/β-catenin signaling pathway
摘要
Abstract
Objective To investigate the effects of aloperine(ALO)on bone metabolism in osteoporosis(OP)mice via Wnt/β-catenin signaling pathway-mediated autophagy and apoptosis.Methods Sixty mice were randomly allocated into six groups(n=10 per group):Sham group(sham-operated mice),OP group(osteoporosis model induced by bilateral ovariectomy),L-ALO group(OP mice intraperitoneally injected with 10 mg/kg aloper-ine),M-ALO group(OP mice intraperitoneally injected with 20 mg/kg aloperine),H-ALO group(OP mice intra-peritoneally injected with 30 mg/kg aloperine),and EV group(OP mice administered 0.09 mg/kg estradiol valerate).Bone mineral density and microstructure of the tibia were assessed.Hematoxylin and eosin(HE)staining was per-formed to examine the morphology of tibial bone tissue.Serum levels of OCN,OPG,ALP,Ca,and P were measured using ELISA.Protein expression levels of LC3-Ⅱ,LC3-Ⅰ,Beclin-1,P62,Caspase-3,Caspase-9,Bax,Wnt3a,β-catenin,and C-Myc were analyzed by Western blot.Autophagosomes were visualized using immunofluorescence.Results Compared with the Sham group,the bone mineral density(BMD)and trabecular thickness in the OP group were significantly reduced,while trabecular separation,bone surface area,and volume were significantly increased(P<0.05).The levels of OPG,OCN,Ca,and P were significantly downregulated,whereas ALP levels were significantly upregulated(P<0.05).Additionally,the LC3-Ⅱ/LC3-Ⅰ ratio and expression levels of Beclin-1,Wnt3a,β-catenin,and C-Myc proteins were significantly decreased,while the expression levels of P62,Caspase-3,Caspase-9,and Bax proteins were significantly increased(P<0.05).Compared with the OP group,the L-ALO,M-ALO,and H-ALO groups exhibited significant increases in BMD and trabecular thickness,along with significant decreases in trabecular separation,bone surface area,and volume(P<0.05).The levels of OPG,OCN,Ca,and P were significantly upregulated,while ALP levels were significantly downregulated(P<0.05).Furthermore,the LC3-Ⅱ/LC3-Ⅰ ratio and expression levels of Beclin-1,Wnt3a,β-catenin,and C-Myc proteins were significantly increased,while the expression levels of P62,Caspase-3,Caspase-9,and Bax proteins were significantly decreased(P<0.05).In contrast,compared with the OP group,the EV group showed significant increases in BMD and trabecular thickness,as well as significant decreases in trabecular separation,bone surface area to volume ratio(P<0.05).The levels of OPG,OCN,Ca,and P were significantly upregulated,while ALP levels were significantly downregulated(P<0.05).Moreover,the LC3-Ⅱ/LC3-Ⅰ ratio and expression levels of Beclin-1,Wnt3a,β-catenin,and C-Myc proteins were significantly increased,while the expression levels of P62,Caspase-3,Caspase-9,and Bax proteins were significantly decreased(P<0.05).Conclusions Peanine may promote autophagy in osteoblasts and inhibit their apoptosis,thereby improving bone metabolism in OP mice.This effect may be mediated through the activation of the Wnt/β-catenin signaling pathway.关键词
苦豆子碱/骨质疏松/Wnt/β-catenin信号通路/自噬/凋亡Key words
aloperine/osteoporosis/Wnt/β-catenin signaling pathway/autophagy/apoptosis分类
中医学引用本文复制引用
肖知周,黄莺,卞华伟..基于Wnt/β-catenin信号通路介导的自噬和凋亡探讨苦豆子碱对骨质疏松小鼠骨代谢的影响[J].实用医学杂志,2025,41(4):500-508,9.基金项目
广东省重点领域研发计划项目(编号:2019B020213001) (编号:2019B020213001)