硒纳米颗粒对类风湿关节炎模型大鼠的治疗效果及抗炎作用机制研究

目的探讨类风湿关节炎(rheumatoid arthritis,RA)模型大鼠应用硒纳米颗粒治疗的效果及可能机制。方法20只雄性SD大鼠,使用Ⅱ型胶原+弗氏完全佐剂制备RA模型,将造模成功19只随机分为RA组10只和硒纳米颗粒组9只。硒纳米颗粒组将硒纳米颗粒6 mg/kg溶于生理盐水灌胃,RA组给予等量生理盐水灌胃,均1次/d,连续3周。灌胃第5、10、15、20天,测量2组足体积,评定关节炎指数,采用Western blot法检测血清谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)、环氧化酶-2(cyclooxygenase-2,COX-2)相对表达量,采用ELISA法检测血清白细胞介素-6(interleukin-6,IL-6)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)相对表达量;灌胃第21天处死大鼠,取踝关节关节软骨以及软骨下骨行组织病理学检查。结果灌胃第5、10、15、20天,硒纳米颗粒组足体积[(2.28±0.16)、(2.87±0.21)、(2.99±0.25)、(2.51±0.18)mL]较RA组[(2.64±0.19)、(3.79±0.27)、(3.98±0.32)、(3.61±0.28)mL]小(P<0.05),关节炎指数(2.12±0.25、6.31±0.72、6.57±0.80、5.26±0.62)较RA组(2.45±0.36、8.26±0.91、9.03±0.82、7.54±0.73)低(P<0.05),血清IL-6表达吸光度值(1.56±0.03、1.48±0.04、1.51±0.03、1.42±0.04)、TNF-α表达吸光度值(1.52±0.03、1.53±0.05、1.46±0.04、1.41±0.03)、COX-2相对表达量(1.39±0.03、1.35±0.03、1.36±0.04、1.31±0.02)较RA组(IL-6:1.85±0.05、1.88±0.03、1.76±0.04、1.92±0.03;TNF-α:1.79±0.04、1.83±0.03、1.82±0.02、1.86±0.03;COX-2:1.59±0.04、1.67±0.05、1.64±0.04、1.66±0.05)低(P<0.05),GSH-Px相对表达量(0.65±0.03、0.69±0.05、0.67±0.04、0.72±0.06)较RA组(0.43±0.03、0.38±0.02、0.39±0.03、0.32±0.02)高(P<0.05);与RA组比较,硒纳米颗粒组大鼠关节滑膜组织受损较轻,细胞排列较为紧密,炎症细胞浸润明显改善。结论硒纳米颗粒可通过调控血清GSH-Px、COX-2、IL-6、TNF-α表达起抗炎作用,有效改善RA模型大鼠病情。

Therapeutic effect and anti-inflammatory mechanism of selenium nanoparticles on rheumatoid arthritis in rat models

Objective To investigate the therapeutic effect and possible mechanism of selenium nanoparticles(SeNPs)in rat models with rheumatoid arthritis.Methods Twenty male SD rats were established rheumatoid arthritis model with typeⅡcollagen and Freund’s complete adjuvant,in which 19 models were successfully established and were randomly divided into RA group(n=10)and SeNPs group(n=9).SeNPs group was given 6 mg/kg SeNPs solution by gavage,and RA group was given the equivalent volume of normal saline by gavage once a day for 3 weeks.The foot volume was measured on the 5 th,10 th,15 th and 20 th days after drug treatment in two groups.The arthritis index was evaluated.The relative expressions of serum glutathione peroxidase(GSH-Px),cyclooxygenase-2(COX-2),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)were detected by Western blot and ELISA.All rats were sacrificed on the 21 st day after drug treatment.The cartilage of ankle joint and subchondral bone were taken for histopathological examination.Results On the 5 th,10 th,15 th and 20 th days after drug treatment,the foot volumes were smaller in SeNPs group((2.28±0.16),(2.87±0.21),(2.99±0.25),(2.51±0.18)mL)than those in RA group((2.64±0.19),(3.79±0.27),(3.98±0.32),(3.61±0.28)mL)(P<0.05);the arthritis indexes were smaller in SeNPs group(2.12±0.25,6.31±0.72,6.57±0.80,5.26±0.62)than those in RA group(2.45±0.36,8.26±0.91,9.03±0.82,7.54±0.73)(P<0.05);the relative expressions of IL-6(1.56±0.03,1.48±0.03,1.51±0.03,1.42±0.04),TNF-α(1.52±0.03,1.53±0.05,1.53±0.05,1.46±0.04,1.41±0.03)and COX-2(1.39±0.03,1.35±0.03,1.36±0.04,1.31±0.02)in SeNPs group were lower than those in RA group(IL-6:1.85±0.05,1.88±0.03,1.76±0.04,1.92±0.03;TNF-α:1.79±0.04,1.83±0.03,1.82±0.02,1.86±0.03;COX-2:1.59±0.04,1.67±0.05,1.64±0.04,1.66±0.05)(P<0.05);the relative expressions of GSH-Px(0.65±0.03,0.69±0.05,0.67±0.04,0.72±0.06)in SeNPs group were higher than those in RA group(0.43±0.03,0.38±0.02,0.39±0.03,0.32±0.02)(P<0.05).Compared with RA group,the damage of synovial tissue was lighter,the cell arrangement was closely arranged,and the infiltration of inflammation cells was significantly improved in SeNPs group.Conclusion SeNPs can effectively improve the severity of RA in rats,and play an anti-inflammatory role by regulating the expressions of GSH-Px,COX-2,IL-6 and TNF-α.