多孔纳米复合材料Se@SiO2治疗激素性股骨头坏死

摘要

背景:激素性股骨头坏死发病率高,预后差,发病机制尚不明确.氧化应激治疗与股骨头坏死的发生发展密切相关.纳米Se具有良好的抗氧化作用.目的:观察多孔纳米复合材料Se@SiO2通过抗氧化应激抑制活性氧对软骨细胞的保护作用,进一步探索抗氧化应激效应在治疗激素性股骨头坏死中的机制.方法:①体外实验:提取、培养并鉴定大鼠软骨细胞,采用多孔纳米复合材料Se@SiO2进行干预培养抑制活性氧产生;②体内动物实验:将36只大鼠随机分为3组,激素诱导组和实验组均采用腹腔注射脂多糖联合肌注甲强龙诱导股骨头坏死,实验组在诱导后第7天给予腹腔注射多孔Se@SiO2干预治疗,对照组为空白对照.诱导坏死后第8周取双侧股骨头行Micro CT扫描分析,苏木精-伊红染色观察.结果与结论:①活性氧检测和TUNEL实验显示:Se@SiO2干预后大鼠软骨细胞中活性氧水平明显降低(P＜0.05);②Micro CT扫描分析:与对照组相比,激素诱导组及实验组骨密度、骨体积、骨表面积/骨体积、骨小梁数、骨小梁分离度、骨小梁厚度差异均有显著性意义(P＜0.05);③苏木精-伊红染色显示,对照组股骨头表面光滑,骨细胞、软骨细胞、骨小梁正常,空骨陷窝和脂肪细胞少见;激素诱导组骨小梁断裂、脂肪细胞肥大融合、出现大量空骨陷窝,有明显骨坏死表现;实验组较激素诱导组股骨头坏死明显好转;④结果表明多孔纳米复合材料Se@SiO2具有良好的抗氧化应激能力,能够抑制活性氧的产生并治疗早期激素性股骨头坏死.%BACKGROUND:Steroid-induced osteonecrosis of the femoral head (SONFH) is a common bone disease characterized as high morbidity and poor prognosis,but the pathogenesis is unclear.Oxidative stress treatment is closely related to the occurrence and development of SONFH,and has tremendous potential in the treatment of SONFH,which can be realized by Nano-Se.OBJECTIVE:To observe the protective effect of porous Se@SiO2 nanocomposite on chondrocytes by antioxidant stress,and to further explore its mechanism of protection and treatment of SONFH.METHODS:(1) In vitro experiment:The rat chondrocytes were isolated,cultured and identified.Then,the chondrocytes were cultured with porous Se@SiO2 nanocomposite to suppress the production of reactive oxygen species (ROS).(2) In vivo experiment:A total of 36 rats were randomly divided into three groups.Steroid-induced group and experimental group were treated with intraperitoneal injection of lipopolysaccharide and intramuscular injection of methylprednisolone to induce SON FH models.Seven days after modeling,the experimental group was intraperitoneally injected with porous Se@SiO2 nanocomposite.No intervention was done in control group (blank control).At 8 weeks after modeling,rat bilateral femoral heads were taken for hematoxylin-eosin staining and Micro-CT scanning.RESULTS AND CONCLUSION:Results from the ROS detection and TUNEL apoptosis tests showed that the level of ROS in the chondrocytes was significantly reduced after intervention with Se@SiO2 (P ＜ 0.05).Micro-CT scanning findings showed that the bone mineral density,bone volume,bone area/bone volume,trabecular number,trabecular thickness,and trabecular separation in the steroid-induced and experimental groups were significantly different from those in the control group (P ＜ 0.05).Hematoxylin-eosin staining results showed smooth femoral head,normal bone cells,chondrocytes and trabecular bone,as well as few empty bone lacunae and fat cells in the control group,while in the steroid-induced group,there was bone trabecular fracture,fat cell hypertrophy fusion,a large number of empty bone lacunae and obvious osteonecrosis.These manifestations were significantly improved in the experimental group.To conclude,the porous Se@SiO2 nanocomposite has good antioxidative stress ability,suppresses the ROS production and exerts therapeutic effects on SONFH.