Shaban Anwaar M, Ali Eman A, Tayel Sara G, Rizk Sara Kamal, El Agamy Dalia F
Medical Physiology Department, Faculty of Medicine, Menoufia University, Menoufia, Egypt.
Clinical Pharmacology Department, Faculty of Medicine, Menoufia University, Menoufia, Egypt.
J Orthop Surg Res. 2025 Jan 9;20(1):25. doi: 10.1186/s13018-024-05344-0.
Castration of adult male rats led to the development of osteoporosis. Oxidative stress and inflammatory factors have been identified as potential causative factors. Notably, oxymatrine (OMT) possesses potent anti-inflammatory and antioxidant activities. This study aims to elucidate the antiosteoporotic effects of OMT compared to testosterone in an orchiectomized (ORX) rat model of osteoporosis.
A total of 60 Wistar male rats were divided into the following groups: control (CTRL), surgery + no orchiectomy (SHAM), ORX, ORX + testosterone, and ORX + OMT. Urinary deoxypyridinoline (DPD), calcium (Ca), and phosphorus (P), as well as serum testosterone, parathormone (PTH), alkaline phosphatase (ALP), osteocalcin, N-telopeptide of type I collagen (NTX I), tartrate resistance acid phosphatase (TRAP), and total Ca and P levels were evaluated. Bone was assessed for malondialdehyde (MDA), reduced glutathione (GSH), interleukin 6 (IL-6), Kelch-like ECH-associated protein 1 (Keap1), nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1) expression, and receptor activator of nuclear factor κB ligand/ osteoprotegerin (RANKL/OPG) ratio. Bone dual-energy X-ray absorptiometry (DEXA) scan and histological and immunohistochemical studies were performed.
Testosterone or OMT treatment ameliorated the reduced bone mineral density (BMD) and bone mineral content (BMC) in the DEXA scan and the changes in PTH and Ca levels. Compared to the ORX group, bone formation, and turnover markers were also significantly reversed in the treatment groups. Treatment with testosterone or OMT significantly reduced bone MDA, IL-6, Keap1, RANKL, and RANKL/OPG ratio, and significantly elevated bone GSH, Nrf2, and HO-1. Moreover, testosterone or OMT treatment has restored cortical bone thickness and osteocyte number and reduced bone levels of TNF-α in ORX rats. Consequently, treatment with either testosterone or OMT exhibited nearly equal therapeutic efficacy; however, neither of them could normalize the measured parameters.
OMT treatment showed equal efficacy compared to testosterone in ameliorating osteoporosis in ORX rats, possibly by improving some inflammatory and oxidative stress parameters.
成年雄性大鼠去势会导致骨质疏松症的发生。氧化应激和炎症因子已被确定为潜在的致病因素。值得注意的是，氧化苦参碱（OMT）具有强大的抗炎和抗氧化活性。本研究旨在阐明在去势（ORX）大鼠骨质疏松模型中，与睾酮相比，OMT的抗骨质疏松作用。
将60只Wistar雄性大鼠分为以下几组：对照组（CTRL）、假手术组（SHAM，手术但未去势）、ORX组、ORX + 睾酮组和ORX + OMT组。检测尿脱氧吡啶啉（DPD）、钙（Ca）和磷（P），以及血清睾酮、甲状旁腺激素（PTH）、碱性磷酸酶（ALP）、骨钙素、I型胶原N-端肽（NTX I）、抗酒石酸酸性磷酸酶（TRAP），以及总Ca和P水平。评估骨组织中的丙二醛（MDA）、还原型谷胱甘肽（GSH）、白细胞介素6（IL-6）、kelch样ECH相关蛋白1（Keap1）、核因子E2相关因子2（Nrf2）、血红素加氧酶1（HO-1）的表达，以及核因子κB受体活化因子配体/骨保护素（RANKL/OPG）比值。进行骨密度双能X线吸收法（DEXA）扫描以及组织学和免疫组织化学研究。
睾酮或OMT治疗改善了DEXA扫描中降低的骨矿物质密度（BMD）和骨矿物质含量（BMC），以及PTH和Ca水平的变化。与ORX组相比，治疗组的骨形成和骨转换标志物也有显著逆转。睾酮或OMT治疗显著降低了骨组织中的MDA、IL-6、Keap1、RANKL以及RANKL/OPG比值，并显著提高了骨组织中的GSH、Nrf2和HO-1水平。此外，睾酮或OMT治疗恢复了ORX大鼠的皮质骨厚度和骨细胞数量，并降低了骨组织中TNF-α的水平。因此，睾酮或OMT治疗显示出几乎相同的治疗效果；然而，它们都不能使测量参数恢复正常。
在改善ORX大鼠骨质疏松方面，OMT治疗与睾酮显示出相同的疗效，可能是通过改善一些炎症和氧化应激参数来实现的。
