Trauma Center, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Institute of Translation Medicine, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Int J Nanomedicine. 2018 Mar 22;13:1809-1818. doi: 10.2147/IJN.S159776. eCollection 2018.
Methylprednisolone (MPS) is an important drug used in therapy of many diseases. However, osteonecrosis of the femoral head is a serious damage in the MPS treatment. Thus, it is imperative to develop new drugs to prevent the serious side effect of MPS.
The potential interferences Se@SiO nanocomposites may have to the therapeutic effect of methylprednisolone (MPS) were evaluated by classical therapeutic effect index of acute respiratory distress syndrome (ARDS), such as wet-to-dry weight ratio, inflammatory factors IL-1β and TNF-α. And oxidative stress species (ROS) index like superoxide dismutase (SOD) and glutathione (GSH) were tested. Then, the protection effects of Se@SiO have in osteonecrosis of the femoral head (ONFH) were evaluated by micro CT, histologic analysis and Western-blot analysis.
In the present study, we found that in the rat model of ARDS, Se@SiO nanocomposites induced SOD and GSH indirectly to reduce ROS damage. The wet-to-dry weight ratio of lung was significantly decreased after MPS treatment compared with the control group, whereas the Se@SiO did not affect the reduced wet-to-dry weight ratio of MPS. Se@SiO also did not impair the effect of MPS on the reduction of inflammatory factors IL-1β and TNF-α, and on the alleviation of structural destruction. Furthermore, micro CT and histologic analysis confirmed that Se@SiO significantly alleviate MPS-induced destruction of femoral head. Moreover, compared with MPS group, Se@SiO could increase collagen II and aggrecan, and reduce the IL-1β level in the cartilage of femoral head. In addition, the biosafety of Se@SiO in vitro and in vivo were supported by cell proliferation assay and histologic analysis of main organs from rat models.
Se@SiO nanocomposites have a protective effect in MPS-induced ONFH without influence on the therapeutic activity of MPS, suggesting the potential as effective drugs to avoid ONFH in MPS therapy.
甲泼尼龙(MPS)是治疗多种疾病的重要药物。然而,股骨头坏死是 MPS 治疗中的严重损伤。因此,开发新的药物来预防 MPS 的严重副作用迫在眉睫。
通过急性呼吸窘迫综合征(ARDS)的经典治疗效果指标,如湿重/干重比、炎症因子 IL-1β 和 TNF-α,评估了 Se@SiO 纳米复合材料对 MPS 治疗效果的潜在干扰。同时还测试了超氧化物歧化酶(SOD)和谷胱甘肽(GSH)等氧化应激指标。然后,通过 micro CT、组织学分析和 Western-blot 分析评估了 Se@SiO 在股骨头坏死(ONFH)中的保护作用。
在本研究中,我们发现,在 ARDS 大鼠模型中,Se@SiO 纳米复合材料间接诱导 SOD 和 GSH 降低 ROS 损伤。与对照组相比,MPS 治疗后肺的湿重/干重比明显降低,而 Se@SiO 对 MPS 降低的湿重/干重比没有影响。Se@SiO 也不影响 MPS 对降低炎症因子 IL-1β 和 TNF-α的作用,以及对结构破坏的缓解作用。此外,micro CT 和组织学分析证实,Se@SiO 显著减轻了 MPS 诱导的股骨头破坏。此外,与 MPS 组相比,Se@SiO 可增加软骨中的胶原 II 和聚集蛋白聚糖,并降低股骨头软骨中的 IL-1β 水平。此外,细胞增殖试验和大鼠模型主要器官的组织学分析支持了 Se@SiO 在体外和体内的生物安全性。
Se@SiO 纳米复合材料对 MPS 诱导的 ONFH 具有保护作用,而不影响 MPS 的治疗活性,提示其有潜力成为避免 MPS 治疗中发生 ONFH 的有效药物。