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| 壮骨止痛方抗骨质疏松大鼠铁死亡及抗斑马鱼铁过载作用 |
| Anti-iron death and anti-zebrafish iron overload effect of Bone Strengthening and Pain Relieving Formula in osteoporotic rats |
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| DOI：10.3969/j.issn.1006-7108.2026.06.015 |
| 中文关键词: 绝经后骨质疏松症 壮骨止痛方 斑马鱼 去卵巢大鼠 铁死亡 铁过载 |
| 英文关键词:postmenopausal osteoporosis Bone Strengthening and Pain Relieving Formula zebrafish ovariectomized rats iron death iron overload |
| 基金项目:国家自然科学基金（81973920）；湖南省自然科学基金（2025JJ90072）；湖南省重点研发计划2024年度项目（2024JK2131）； 湖南省卫生健康委科研项目（D202303107310）；长沙市自然科学基金（kq2502220）；湖南中医药大学校级研究生创新项目（2023CX170） |
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| 中文摘要: |
| 目的 观察壮骨止痛方对去卵巢大鼠与铁过载斑马鱼骨质疏松症的影响，探讨其在调控铁死亡途径的潜在作用。方法 通过双侧卵巢切除术制备绝经后骨质疏松大鼠模型，随机分为模型（OVX）组、壮骨止痛方中剂量组（ZGZTM）、壮骨止痛方高剂量组（ZGZTH）、雌二醇（EV）组、假手术（SHAM）组。运用HE和电镜观察大鼠胫骨形态学；ELISA测定大鼠血清铁蛋白、总铁离子、亚铁离子、丙二醛水平；普鲁士蓝检测大鼠肝、骨组织铁沉积水平；免疫组化检测TF表达，免疫荧光检测ACSL4和GPX4表达；RT-qPCR检测GPX4、TF、ACSL4、RUNX2 mRNA表达；Western Blot检测GPX4、TF、ACSL4、RUNX2蛋白表达。通过枸橼酸铁铵（FAC）诱导2dpf斑马鱼骨质疏松症模型，运用茜素红染色观察斑马鱼头骨形态。结果 相对SHAM组，去卵巢大鼠微结构被破坏，灌胃壮骨止痛方后，骨微细结构改善。模型组血清铁蛋白、丙二醛、总铁离子、亚铁离子含量上升（P<0.05），TF、ACSL4蛋白及mRNA表达增加，GPX4下调，治疗后，以上指标变化均缓解（P<0.05）；普鲁士蓝检测结果显示，OVX组大鼠肝与骨组织铁沉积较重，用药后减轻。与空白组相比， FAC组茜素红染色面积显著下降（P<0.05），用药后，染色面积显著增加（P<0.05）。结论 壮骨止痛方能够抑制绝经后骨质疏松大鼠骨组织中脂质过氧化含量与铁沉积铁代谢水平，能抑制枸橼酸铁铵诱导的铁过载导致的斑马鱼骨质疏松作用，通过抑制铁死亡通路缓解绝经后骨质疏松可能是壮骨止痛方调节骨代谢的机制之一。 |
| 英文摘要: |
| Objective To observe the effects of Bone Strengthening and Pain Relieving Formula on osteoporosis in ovariectomized rats with iron overloaded zebrafish, and to explore its potential role in regulating the iron death pathway. Methods Bilateral ovariectomy was conducted to prepare a rat PMOP model. Drug gavage was performed for 12 weeks. HE and electron microscopy were used to observe the morphology of rat tibia. ELISA was used to determine the levels of serum ferritin, total ferrous iron, ferrous iron, and malondialdehyde in rats. Prussian blue was used to examine the levels of iron deposition in the liver and bone tissues of rats. Immunohistochemistry was used to examine the expression of TF. Immunofluorescence was used to examine the expressions of ACSL4 and GPX4. RT-qPCR was used to detect mRNA expressions of GPX4, TF, ACSL4, and RUNX2. Western blotting was used to detect protein expressions of GPX4, TF, ACSL4, and RUNX2. Ferric ammonium citrate (FAC) was used to induce the 2dpf zebrafish osteoporosis model. Alizarin red staining was used to observe zebrafish skull morphology. Results The microstructure was destroyed in the relative SHAM group of ovariectomised rats. The bone microstructure was improved after the administration of Bone Strengthening and Pain Relieving Formula. Serum ferritin, malondialdehyde, total ferric ion, and ferrous ion content increased in the model group (P<0.05). TF and ACSL4 protein and mRNA expression increased. GPX4 was down-regulated. After the treatment, the changes of the above indexes were relieved (P<0.05). Prussian blue results showed that iron deposition in the liver and bone tissues of rats in the OVX group was heavier, which was alleviated by the administration of the drug. Compared to that in the blank group, the area of Alizarin red staining in the FAC group decreased significantly (P<0.05). After the administration of the drug, the staining area increased significantly (P<0.05). Conclusion Bone Strengthening and Pain Relieving Formula inhibits lipid peroxidation content and iron deposition in bone tissues and iron metabolism level of postmenopausal osteoporotic rats, and inhibits the effect of iron overload induced by ferric ammonium citrate on osteoporosis in zebrafish. The alleviation of postmenopausal osteoporosis by inhibiting the iron death pathway may be one of the mechanisms by which Bone Strengthening and Pain Relieving Formula regulates the bone metabolism. |
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