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| 依帕司他靶向氧化应激改善去卵巢小鼠骨质疏松研究 |
| Therapeutic effects of epalrestat on ovariectomy-induced osteoporosis in mice |
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| DOI：10.3969/j.issn.1006-7108.2026.06.017 |
| 中文关键词: 依帕司他 骨质疏松 氧化应激 卵巢摘除术 |
| 英文关键词:epalrestat osteoporosis oxidative stress ovariectomy |
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| 中文摘要: |
| 目的 探究依帕司他（Epalrestat）对去卵巢小鼠骨质疏松的作用及其可能存在的骨保护机制。方法 将25只8周龄C57BL/6雌性小鼠随机分为假手术组（sham）、模型组（con）、依帕司他低（Epa-L）、中（Epa-M）、高剂量组（Epa-H），每组5只。从3周龄小鼠股骨中提取骨髓间充质干细胞（BMSCs），通过CCK-8实验检测依帕司他对小鼠骨髓间充质干细胞活力的影响。利用去卵巢方法构建骨质疏松模型小鼠，模型制备成功后假手术组用生理盐水灌胃，其余组用相应剂量依帕司他灌胃。连续8周后，通过对股骨组织进行 Micro?CT检测、HE染色，分别观察小鼠骨密度、骨组织病理形态。运用Western blot 检测小鼠组织 Runx2、ALP、Col1α1、OPG、TNF-α、TGF-β1、IL-6、IL-1β的蛋白表达情况。结果 模型组小鼠股骨组织的Micro?CT显示，依帕司他能增加骨小梁密度；其中中、高剂量组具有显著统计学意义( P<0. 01, P<0. 05) 。HE染色结果显示依帕司他加药组可明显改善骨小梁的的病理变化；Western blot结果提示加药组中 Runx2、ALP、Col1α1、OPG蛋白表达明显升高，TNF-α、TGF-β1、IL-6、IL-1β蛋白表达明显降低。结论 依帕司他可以改善去卵巢骨质疏松模型小鼠的骨微结构，其发挥抗骨质疏松作用可能与减少小鼠体内氧化应激反应有关。 |
| 英文摘要: |
| Objective To determine the therapeutic potential of epalrestat against osteoporosis in ovariectomized (OVX) mice and the cellular mechanisms of its action. Methods A cohort of twenty five 8-week-old female C57BL/6 mice was randomly assigned to five groups (n=5/group): sham-operated (Sham), OVX control (OVX-Con), and OVX groups gavaged with low- (Epa-L), medium- (Epa-M), or high-dose (Epa-H) of epalrestat. Bone marrow-derived mesenchymal stem cells (BMSCs) were isolated from 3-week-old mice, and the compound's effect on BMSC proliferation was evaluated using an EdU assay. An osteoporotic phenotype was induced via bilateral ovariectomy. After successful model validation, the designated groups received epalrestat orally for 8 weeks. The controls received an equal volume of normal saline. After the intervention, femoral bone mineral density (BMD) and histopathological morphology were analyzed with micro-CT and HE staining, respectively. The protein expression levels of Runx2, ALP, Col1α1, OPG, TNF-α, TGF-β1, IL-6, and IL-1β were detected wutg Western blotting. Results Micro-CT analysis of femoral tissues indicated that epalrestat treatment significantly enhanced trabecular bone density compared to the OVX-Con group. This increase was statistically significant in the medium- and high-dose cohorts (P<0.01 and P<0.05, respectively). HE staining revealed a notable amelioration of pathological alterations in the trabecular bone microstructure following epalrestat administration. Western blotting analysis demonstrated a marked upregulation of osteogenic markers (Runx2, ALP, Col1α1, OPG) and a significant downregulation of proteins associated with oxidative stress and inflammation (TNF-α, TGF-β1, IL-6, IL-1β) in the treatment groups. Conclusion Epalrestat confers protective effects on bone microstructure in OVX-induced osteoporotic mice. The anti-osteoporotic efficacy is potentially mediated through the attenuation of oxidative stress. |
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