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| 壮骨方通过System Xc /GPX4轴调控铁过载干预绝经后骨质疏松症 |
| Zhuanggu Fang intervenes in postmenopausal osteoporosis by regulating iron overload through the System Xc-/GPX4 axis |
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| DOI：10.3969/j.issn.1006-7108.2026.08.005 |
| 中文关键词: 绝经后骨质疏松症 壮骨方 铁过载 System Xc-/GPX4通路 |
| 英文关键词:postmenopausal osteoporosis Zhuanggu Fang iron overload System Xc-/GPX4 pathway |
| 基金项目:广西自然科学基金（2024GXNSFBA010316）；广西自然科学基金（2025GXNSFAA069972）；国家自然科学基金地区基金（82360869） |
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| 中文摘要: |
| 目的 探讨壮骨方（Zhuanggu Fang ，ZGF）激活System Xc-/GPX4信号轴调控铁过载干预绝经后骨质疏松症（postmenopausal osteoporosis，PMOP）的机制研究。方法 70只雌性SD大鼠，随机分为假手术组（Sham组，n=15）、造模组(（n=55）。造模组大鼠全部采用去势造模法构建PMOP模型，模型评价成功后将大鼠随机分为去卵巢组、阳性对照组、ZGF低、中、高剂量组。药物干预12周之后取材，采用微型计算机断层扫描（Micro-CT）评估股骨骨质量变化；抗酒石酸酸性磷酸酶染色（TRAP）和免疫荧光法观察骨稳态变化；酶标仪检测骨组织中丙二醛（MDA）和谷胱甘肽（GSH）含量便于观测氧化应激与脂质过氧化；ELISA法测定骨组织中铁蛋白含量变化；RT-qPCR和Western-blot法检测股骨System Xc-/GPX4信号轴关键分子表达水平。结果 与Sham组比较，OVX组大鼠骨微结构指标BV/TV、Tb.Th和Tb.N显著降低（P<0.01），Tb.Sp、SMI显著升高（P<0.01）；骨小梁断裂，骨髓腔扩大；破骨细胞数量及标志物、MDA及铁蛋白含量明显提高（P<0.01）；成骨细胞标志物及GSH含量显著减少（P<0.01）；大鼠骨组织中SLC7A11 、SLC3A2及GPX4蛋白和mRNA表达水平明显降低（P<0.01）。与OVX组比较，ZGF高剂量组大鼠骨微结构指标Tb.N明显升高（P<0.01），Tb.Sp、SMI显著降低（P<0.05）；破骨细胞数量及标志物、MDA及铁蛋白含量明显降低（P<0.01）；成骨细胞标志物及GSH含量显著升高（P<0.01）；大鼠骨组织中SLC7A11 、SLC3A2及GPX4蛋白和mRNA表达水平明显升高（P<0.01）。结论 ZGF可增加去卵巢大鼠骨体积分数和骨小梁数量，上调Osterix、OCN表达水平，下调破骨细胞标志因子TRAF6表达水平，抑制破骨细胞活性；并上调SLC7A11、SLC3A2、GSH、GPX4，下调MDA，抑制铁过载干预破骨细胞分化，从而干预PMOP的进程。 |
| 英文摘要: |
| Objective To investigate the mechanism by which Zhuanggu Fang (ZGF) activates the System Xc-/GPX4 signaling axis to regulate iron overload and intervene in postmenopausal osteoporosis(PMOP). Methods Seventy female SD rats were randomly divided into a sham-operated group (Sham, n=15) and a modeling group (n=55). All rats in the modeling group underwent ovariectomy to establish the PMOP model. After successful model evaluation, the rats were randomly assigned into the ovariectomized group, positive control group, and ZGF low-, medium-, and high-dose groups. After 12 weeks of drug intervention, femoral samples were collected. Bone quality changes were assessed by micro-computed tomography (Micro-CT). Bone homeostasis was observed by tartrate-resistant acid phosphatase (TRAP) staining and immunofluorescence. Malondialdehyde (MDA) and glutathione (GSH) levels in bone tissue were measured using a microplate reader to evaluate oxidative stress and lipid peroxidation. Ferritin levels in bone tissue were determined by ELISA. The expression of key molecules of the System Xc-/GPX4 signaling axis in the femur was detected by RT-qPCR and Western blot. Results Compared with the Sham group, bone microstructural parameters including BV/TV, Tb.Th, and Tb.N were significantly decreased in the OVX group（P<0.01）, while Tb.Sp and SMI were significantly increased（P<0.01）. Trabecular fractures and marrow cavity expansion were observed. The number of osteoclasts, osteoclast markers, MDA, and ferritin levels were markedly increased, whereas osteoblast markers and GSH levels were significantly decreased. Expression of SLC7A11, SLC3A2, and GPX4 proteins and mRNAs in bone tissue was significantly downregulated（P<0.01）. Compared with the OVX group, rats in the high-dose ZGF group showed significantly increased Tb.N（P<0.01）, and significantly decreased Tb.Sp and SMI（P<0.01）. The number of osteoclasts, osteoclast markers, MDA, and ferritin levels were markedly reduced, while osteoblast markers and GSH levels were significantly increased（P<0.01）. Expression of SLC7A11, SLC3A2, and GPX4 proteins and mRNAs in bone tissue was significantly upregulated（P<0.01）. Conclusion ZGF can increase bone volume fraction and trabecular number in ovariectomized rats, upregulate Osterix and OCN expression, downregulate the osteoclast marker TRAF6, and inhibit osteoclast activity. Furthermore, ZGF upregulates SLC7A11, SLC3A2, GSH, and GPX4 while downregulating MDA, thereby suppressing iron overload–induced osteoclast differentiation and intervening in the progression of PMOP. |
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