Yang Xinlin, Jin Li, Yao Lu, Shen Francis H, Shimer Adam L, Li Xudong
Orthopaedic Research Laboratories, University of Virginia, Charlottesville, VA, USA.
School of Life Science, Beijing Institute of Technology, Beijing, People's Republic of China ; Research Institute of Beijing Tongrentang Co., Ltd, Beijing, People's Republic of China.
Int J Nanomedicine. 2014 May 15;9:2419-30. doi: 10.2147/IJN.S60853. eCollection 2014.
Compelling evidence suggests that reactive oxygen species (ROS) play a pivotal role in disk degeneration. Fullerol nanoparticles prepared in aqueous solution have been demonstrated to have outstanding ability to scavenge ROS. In this report, in vitro and in vivo models were used to study the efficacy of fullerol in preventing disk degeneration. For in vitro experiments, a pro-oxidant H2O2 or an inflammatory cytokine interleukin (IL)-1β was employed to induce degenerated phenotypes in human nucleus pulposus cells encapsulated in alginate beads, and fullerol was added in the culture medium. For the animal study, an annulus-puncture model with rabbit was created, and fullerol was injected into disks. It was shown that cytotoxicity and cellular ROS level induced by H2O2 were significantly diminished by fullerol. IL-1β-induced nitric oxide generation in culture medium was suppressed by fullerol as well. Gene-profile and biochemical assays showed that fullerol effectively reversed the matrix degradation caused by either H2O2 or IL-1β. The animal study delineated that intradiskal injection of fullerol prevented disk degeneration, increasing water and proteoglycan content and inhibiting ectopic bone formation. These results suggest that antioxidative fullerol may have a potential therapeutic application for disk degeneration.
有力证据表明,活性氧(ROS)在椎间盘退变中起关键作用。已证明在水溶液中制备的富勒醇纳米颗粒具有出色的清除ROS的能力。在本报告中,使用体外和体内模型研究富勒醇预防椎间盘退变的功效。对于体外实验,使用促氧化剂过氧化氢(H2O2)或炎性细胞因子白细胞介素(IL)-1β诱导包裹在藻酸盐珠中的人髓核细胞出现退变表型,并在培养基中添加富勒醇。对于动物研究,建立了兔椎间盘穿刺模型,并将富勒醇注入椎间盘。结果表明,富勒醇可显著降低H2O2诱导的细胞毒性和细胞ROS水平。富勒醇也抑制了IL-1β诱导的培养基中一氧化氮的生成。基因谱和生化分析表明,富勒醇有效地逆转了由H2O2或IL-1β引起的基质降解。动物研究表明,椎间盘内注射富勒醇可预防椎间盘退变,增加水分和蛋白聚糖含量,并抑制异位骨形成。这些结果表明,具有抗氧化作用的富勒醇可能对椎间盘退变具有潜在的治疗应用价值。