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多孔 Se@SiO 纳米复合材料可保护股骨头免受甲泼尼龙诱导的骨坏死。

Porous Se@SiO nanocomposites protect the femoral head from methylprednisolone-induced osteonecrosis.

机构信息

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.

出版信息

Int J Nanomedicine. 2018 Mar 22;13:1809-1818. doi: 10.2147/IJN.S159776. eCollection 2018.

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

摘要

背景

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。

方法

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。

结果

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。

结论

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f805/5868597/91754f07c4e2/ijn-13-1809Fig1.jpg

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