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| GDF15对绝经后妇女血脂与骨代谢的调节作用研究 |
| The regulatory role of growth differentiation factor 15 in blood lipid and bone metabolism in postmenopausal women |
| 投稿时间：2025-04-16 |
| DOI：10.3969/j.issn.1000-0399.2025.11.002 |
| 中文关键词: 生长分化因子15 绝经后妇女 脂类代谢 骨密度 |
| 英文关键词: Growth differentiation factor 15 Postmenopausal women Lipid metabolism Bone density |
| 基金项目:国家自然科学基金资助项目(编号:82170697),国家自然科学基金资助项目(编号:82400821), 陕西省自然科学基金资助项目(编号:2024JC-YBQN-0961), 陕西省重点研发计划项目(编号:2023-YBSF-330) |
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| 中文摘要: |
| 目的 探讨生长分化因子15(GDF15)对绝经后妇女血脂和骨代谢的调节作用及机制。方法 选取2022年12月至2024年12月于西安交通大学第二附属医院肾病科、神经内科及妇产科住院的160例自然绝经≥1年的妇女（年龄47～80岁）为研究对象，采用酶联免疫吸附测定（ELISA）法检测血清GDF15水平，全自动生化分析仪测定血脂指标总胆固醇（TC）、三酰甘油（TG）、高密度脂蛋白（HDL）、低密度脂蛋白（LDL），双能X射线骨密度仪测量骨密度（BMD）及体脂；通过Pearson相关性分析及多元线性回归分析指标间关联性。动物实验将28只C57BL/6小鼠随机分为对照组（n=7）、GDF15组（n=7）、去卵巢（OVX）组（n=7）及OVX+GDF15组（n=7），予重组GDF15(4 nmol/kg)干预8周，ELISA法检测小鼠血清血脂水平。细胞实验评估GDF15(50 ng/mL)对骨髓间充质干细胞（BMSC）成骨/成脂分化的影响。结果 临床研究结果显示，GDF15与髋关节BMD呈正相关（r=0.197, P=0.013），与TC(r=-0.229, P=0.004)和LDL(r=-0.462,P<0.001)呈负相关，与TG和体脂无显著关联；多元线性回归分析结果显示，GDF15为LDL的独立预测因子（β=-1.264,P<0.05）。动物实验结果表明，GDF15降低OVX小鼠的TC和LDL水平（P<0.05），但对TG无影响。细胞实验证实GDF15促进BMSC成骨分化，抑制成脂分化。结论 GDF15可能通过选择性降低TC和LDL及促进骨形成改善绝经后代谢紊乱，其对TG和体脂影响有限，提示其在脂代谢和骨代谢中的特异性作用，为相关疾病治疗提供了新方向。 |
| 英文摘要: |
| Objective To investigate the regulatory effects of growth differentiation factor 15（GDF15） on lipid metabolism and bone metabolism in postmenopausal women and the underlying mechanism. Methods Clinical study: From December 2022 to December 2024, 160 naturally postmenopausal women（aged 47～80 years, ≥1 year postmenopause） hospitalized in the Departments of Nephrology, Neurology, and Gynecology ＆ Obstetrics at the Second Affiliated Hospital of Xi’an Jiaotong University were enrolled. Serum GDF15 levels were measured by ELISA. Lipid profiles—including total cholesterol（TC）, triglycerides（TG）, high-density lipoprotein（HDL）, and low-density lipoprotein（LDL）—were analyzed using an automated biochemical analyzer. Bone mineral density and body fat were assessed by dual-energy X-ray absorptiometry. The associations were evaluated using Pearson correlation and multiple linear regression analyses. Animal experiment: Twentyeight C57 BL/6 mice were divided into four groups: Control, GDF15, ovariectomized（OVX）, and OVX+GDF15. Recombinant GDF15（4 nmol/kg） was administered for 8 weeks, followed by serum lipid measurement via ELISA. Cell experiment: The impact of GDF15（50 ng/mL） on osteogenic/adipogenic differentiation of bone marrow mesenchymal stem cells（BMSCs） was evaluated. Results Clinical: GDF15 was positively correlated with hip BMD（r=0.197, P=00.013） but negatively with TC（r=-0.229, P＜0.01） and LDL（r=-0.462, P＜0.05）. No significant associations were observed with TG or body fat. Multiple linear regression confirmed GDF15 as an independent predictor of LDL（β=-1.264, P＜0.05）. Animal: GDF15 reduced TC and LDL levels in OVX mice（P＜0.05）, with no effect on TG cell. GDF15 promoted BMSC osteogenic differentiation and suppressed adipogenic differentiation. Conclusion GDF15 may ameliorate postmenopausal metabolic disorders by selectively reducing TC/LDL and promoting bone formation, while exhibiting limited effects on TG and body fat. These findings suggest its specific roles in lipid and bone metabolism, providing new insights for therapeutic strategies. |
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