Lu Hanli, Gan Nannan, Du Jun, Xue Tianle, Hou Desheng, Lu Cheng
Department of Orthopedics, The First People's Hospital of Chuzhou City, Clinic Medical College of Anhui Medical University, Chuzhou, China.
Department of Laboratory, The First People's Hospital of Chuzhou City, Clinic Medical College of Anhui Medical University, Chuzhou, China.
Ann Med. 2025 Dec;57(1):2512627. doi: 10.1080/07853890.2025.2512627. Epub 2025 Jun 2.
This research aimed to examine the possible impacts of Melatonin (Mel) combined with static magnetic field (SMF) on bone mass and strength in rats with osteoporosis induced by bilateral ovary removal.
Following bilateral ovariectomy, the female ovariectomized (OVX) rats were systematically allocated into four distinct experimental groups: (1) OVX (control group), (2) OVX+melatonin (OVX+Mel), (3) OVX+magnetostatic field (OVX+SMF), and (4) OVX+melatonin/magnetostatic field (OVX+Mel/SMF). The intervention protocol consisted of daily administration of melatonin (30 mg/kg/day), exposure to a static magnetic field (50 ± 4 µT), or a combination of both treatments for a duration of 12 weeks. Upon completion of the treatment period, comprehensive biological samples were collected, including blood specimens and bilateral femurs, for subsequent multi-modal analyses. These analyses encompassed Micro-CT imaging for bone microarchitecture evaluation, histological examination for tissue morphology, biomechanical testing for bone strength assessment, serum cytokine profiling, oxidative stress marker quantification, bone metabolic marker analysis, and RT-PCR for gene expression evaluation.
Micro-CT evaluation indicated that OVX rats treated with Mel and SMF had significantly higher BMD, BMC BV/TV, Tb. N, and Tb. Th values, along with lower Tb. Sp than the OVX+SMF and OVX+Mel groups (all < 0.05). Histological analysis showed that the combination of Mel and SMF notably improved trabecular quality while increasing MAR, OC, and SOD2 expression, and reducing TRAP and TNF-α levels compared to the OVX+SMF and OVX+Mel groups (all < 0.05). Biomechanical tests demonstrated that combined treatment enhanced maximum load, stiffness, energy absorption, ultimate stress, toughness, and elastic modulus in comparison to the OVX+SMF and OVX+Mel groups (all < 0.05). RT-PCR results revealed a significant increase in SIRT1 and OPG expression while inhibiting RANKL and SOST compared to the OVX+SMF and OVX+Mel groups (all < 0.05). Serum tests found that this combination treatment significantly reduced levels of P1NP, CTX-1, MDA, TNF-α, and IL-6 while increasing SOD expression relative to the OVX+SMF and OVX+Mel groups (all < 0.05).
Our results indicate that Mel combined with SMF has the potential to be an effective method for preventing bone loss and maintaining bone strength in postmenopausal osteoporosis.
本研究旨在探讨褪黑素(Mel)联合静磁场(SMF)对双侧卵巢切除所致骨质疏松大鼠骨量和骨强度的可能影响。
双侧卵巢切除术后,将雌性去卵巢(OVX)大鼠系统地分为四个不同的实验组:(1)OVX(对照组),(2)OVX+褪黑素(OVX+Mel),(3)OVX+静磁场(OVX+SMF),以及(4)OVX+褪黑素/静磁场(OVX+Mel/SMF)。干预方案包括每日给予褪黑素(30 mg/kg/天)、暴露于静磁场(50 ± 4 µT)或两种治疗方法联合使用,持续12周。治疗期结束后,收集包括血液样本和双侧股骨在内的综合生物样本,用于后续的多模式分析。这些分析包括用于骨微结构评估的Micro-CT成像、用于组织形态学的组织学检查、用于骨强度评估的生物力学测试、血清细胞因子谱分析、氧化应激标志物定量、骨代谢标志物分析以及用于基因表达评估的RT-PCR。
Micro-CT评估表明,接受Mel和SMF治疗的OVX大鼠的骨密度、骨矿含量、骨体积分数、骨小梁数量和骨小梁厚度值显著高于OVX+SMF组和OVX+Mel组,而骨小梁间距低于这两组(均P < 0.05)。组织学分析显示,与OVX+SMF组和OVX+Mel组相比,Mel和SMF联合使用显著改善了骨小梁质量,并增加了矿化沉积率、骨钙素和超氧化物歧化酶2(SOD2)的表达,同时降低了抗酒石酸酸性磷酸酶和肿瘤坏死因子-α(TNF-α)水平(均P < 0.05)。生物力学测试表明,与OVX+SMF组和OVX+Mel组相比,联合治疗提高了最大负荷、刚度、能量吸收、极限应力、韧性和弹性模量(均P < 0.05)。RT-PCR结果显示,与OVX+SMF组和OVX+Mel组相比,沉默信息调节因子1(SIRT1)和骨保护素(OPG)的表达显著增加,而核因子κB受体活化因子配体(RANKL)和硬化蛋白(SOST)的表达受到抑制(均P < 0.05)。血清检测发现,与OVX+SMF组和OVX+Mel组相比,这种联合治疗显著降低了I型前胶原氨基端前肽(P1NP)、I型胶原交联C-末端肽(CTX-1)、丙二醛(MDA)、TNF-α和白细胞介素-6(IL-6)的水平,同时增加了SOD的表达(均P < 0.05)。
我们的结果表明,Mel联合SMF有可能成为预防绝经后骨质疏松症骨丢失和维持骨强度的有效方法。