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| 高脂高糖联合华法林钠诱导大鼠血管钙化与骨质疏松共病模型的研究 |
| Study on the rat model of vascular calcification and osteoporosis comorbidity induced by a combined high-fat and high-sucrose diet and warfarin sodium |
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| DOI：10.3969/j.issn.1006-7108.2026.03.003 |
| 中文关键词: 动物模型 高脂高糖饮食 华法林钠 血管钙化 骨质疏松 |
| 英文关键词:animal model high-fat high-sucrose diet warfarin sodium vascular calcification osteoporosis |
| 基金项目:福建省自然科学基金资助项目（2022J011091） |
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| 中文摘要: |
| 目的 构建高脂高糖联合华法林钠诱导的大鼠血管钙化与骨质疏松共病模型，并探讨OPG/RANKL及BMP2/Runx2信号通路在血管组织中的作用潜力。方法 20只雄性SD大鼠随机分为对照组（n=10）和模型组（n=10）。模型组喂饲高脂饲料（45 %脂肪）和5 %葡萄糖水，每日皮下注射华法林钠（150 mg/kg）及维生素K1（15 mg/kg），12 h后追加华法林钠（150 mg/kg）；对照组喂饲普通饲料和普通饮用水，每日注射等量生理盐水。造模8周。8周后杀检取材，通过Von Kossa染色观察胸主动脉钙沉积；通过全自动生化分析仪检测血钙、肝功能（肌酐、尿素氮）、肾功能（白蛋白、碱性磷酸酶、谷草转氨酶）；通过ELISA法检测血清中PINP和CTX-I的表达；通过免疫组织化学染色检测胸主动脉OPG、RANKL、BMP2和Runx2蛋白表达；通过DXA测定右后肢股骨干骨密度。结果 模型组胸主动脉出现大量黑色钙化斑块，对照组未见明显钙化；模型组血清钙水平显著高于对照组（P<0.05），肝肾功能指标无显著变化；模型组血清PINP和CTX-I水平显著升高（P<0.05）；模型组胸主动脉OPG蛋白表达下降，RANKL、BMP2和Runx2蛋白表达升高；模型组股骨干近膝关节段骨密度显著下降（P<0.05）。结论 高脂高糖联合华法林钠可成功诱导大鼠血管钙化伴股骨干近膝段骨质疏松，其病理过程与血管组织中OPG/RANKL失衡及BMP2/Runx2信号异常激活密切相关，提示二者可能作为共病治疗的潜在靶点。 |
| 英文摘要: |
| Objective To establish a rat model of vascular calcification comorbidity with osteoporosis induced by a high-fat high-sucrose diet combined with warfarin sodium, and to explore the potential roles of the OPG/RANKL and BMP2/Runx2 signaling pathways in vascular tissues. Methods Twenty male Sprague-Dawley rats were randomly divided into a control group (n=10) and a model group (n=10). Rats in the model group received a high-fat diet (45% fat) and 5% glucose water, with daily subcutaneous injections of warfarin sodium (150 mg/kg) and vitamin K1 (15 mg/kg), followed by an additional warfarin sodium (150 mg/kg) 12 hours later. Rats in the control group received standard chow, plain water, and equivalent volumes of saline injections daily. The modeling period lasted for 8 weeks. Post-sacrifice, thoracic aortas were harvested for calcium deposition assessment via von Kossa staining. Serum calcium, hepatic function markers (creatinine, urea nitrogen), renal function markers (albumin, alkaline phosphatase, aspartate aminotransferase), and bone turnover markers (PINP and CTX-I) were measured using an automated biochemical analyzer and ELISA. Immunohistochemical staining was performed to evaluate OPG, RANKL, BMP2, and Runx2 protein expressions in aortic tissues. Bone mineral density (BMD) of the proximal knee segment of the right femur was determined with dual-energy X-ray absorptiometry (DEXA). Results The model group exhibited extensive black calcified plaques in the thoracic aorta, which were absent in controls. Serum calcium levels were significantly elevated in the model group (P<0.05), while hepatic and renal function parameters showed no significant differences. Serum PINP and CTX-I levels increased markedly in the model group (P<0.05). Aortic tissues from the model group displayed reduced OPG expression and up-regulated RANKL, BMP2, and Runx2 expressions. Additionally, BMD in the proximal femoral segment adjacent to the knee joint was significantly reduced in the model group (P<0.05). Conclusion The combined intervention of a high-fat high-sucrose diet and warfarin sodium successfully induced vascular calcification with concomitant osteoporosis in the proximal femoral segment of rats. This pathological progression is closely linked to OPG/RANKL imbalance and abnormal activation of the BMP2/Runx2 signaling pathway in vascular tissues, highlighting these pathways as potential therapeutic targets for managing this comorbidity. |
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