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软组织肉瘤和阿霉素对小鼠骨代谢的影响。

Effects of Soft Tissue Sarcoma and Doxorubicin on Bone Metabolism in Mice.

机构信息

Department of Orthopedic Surgery, Akita University Graduate School of Medicine, Akita, Japan

Department of Orthopedic Surgery, Akita University Graduate School of Medicine, Akita, Japan.

出版信息

In Vivo. 2023 Jul-Aug;37(4):1532-1539. doi: 10.21873/invivo.13238.

Abstract

BACKGROUND/AIM: This study aimed to evaluate the effects of doxorubicin (Dox) on bone microstructure and metabolism in a mouse model of soft tissue sarcoma.

MATERIALS AND METHODS

CCRF S-180II cells (2-4×10 cells/0.2 ml) were injected subcutaneously into the back of mice. The mice were divided into four groups according to tumor and treatment status and were reared and sacrificed after 2 or 4 weeks. Micro-computed tomography (CT) was performed to calculate the architecture of the femoral bone. The proximal tibia was double stained with tartrate-resistant acid phosphatase (TRACP) and alkaline phosphatase (ALP), and bone morphometry was performed.

RESULTS

Trabecular bone mass was significantly reduced in the Sarcoma and Sarcoma+Dox groups. Cortical bone thickness was reduced in the DOX group, with a stronger effect observed in the Sarcoma+Dox group. In bone morphometry, osteoclast number at the bone surface (Oc.N/BS) was significantly lower in the Dox, Sarcoma, and Sarcoma+Dox groups than in the Control group at 2 weeks. The osteoblast surface at the bone surface (Ob.S/BS) was significantly lower in the Dox and Sarcoma groups than in the Control group at 2 weeks. At 4 weeks, the differences were smaller for both Oc.N/BS and Ob.S/BS.

CONCLUSION

The use of doxorubicin alone worsened the cortical bone structure; however, the presence of both soft-tissue sarcoma and doxorubicin use worsened both cortical and trabecular bone structures from an early stage.

摘要

背景/目的:本研究旨在评估阿霉素(Dox)对软组织肉瘤小鼠模型中骨微结构和代谢的影响。

材料和方法

将 CCRF S-180II 细胞(2-4×10 个细胞/0.2 ml)皮下注射到小鼠背部。根据肿瘤和治疗情况将小鼠分为四组,在 2 或 4 周后进行饲养和处死。进行微计算机断层扫描(CT)以计算股骨的结构。用抗酒石酸酸性磷酸酶(TRACP)和碱性磷酸酶(ALP)对胫骨近端进行双重染色,并进行骨形态计量学分析。

结果

肉瘤和肉瘤+Dox 组的小梁骨量明显减少。DOX 组皮质骨厚度减少,肉瘤+Dox 组的影响更强。在骨形态计量学中,2 周时 Dox、肉瘤和肉瘤+Dox 组的骨表面破骨细胞数(Oc.N/BS)明显低于对照组。2 周时 Dox 和肉瘤组的骨表面成骨细胞表面积(Ob.S/BS)明显低于对照组。4 周时,Oc.N/BS 和 Ob.S/BS 的差异较小。

结论

单独使用阿霉素会使皮质骨结构恶化;然而,从早期开始,既有软组织肉瘤又有阿霉素使用会使皮质骨和小梁骨结构都恶化。

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