一氧化氮合酶抑制剂调控白细胞介素1β和脂多糖对关节软骨的损害  

Modulation of inducible nitric oxide synthase inhibitors on articular cartilage damage after intraarticular injection of interleukin-1β and lipopolysaccharides in rabbits

作　　者：王吉兴[1] 孙炜[1] 金大地[1] 

机构地区：[1]第一军医大学附属南方医院脊柱骨病科,广州510515

出　　处：《中华风湿病学杂志》2002年第1期21-24,T001,共5页Chinese Journal of Rheumatology

基　　金：国家自然科学基金资助项目 ( 3990 0 14 9)

摘　　要：目的　评价兔膝关节内注射白细胞介素 1β (IL 1β)和脂多糖 (LPS)混合液后 ,一氧化氮合酶 (iNOS)抑制剂S 甲基异硫脲 (SMT)调控关节软骨代谢的作用。方法　实验分为 3组 ,正常组 :不使用任何干预药物 ;对照组 :皮下注射生理盐水后 ,膝关节内给予白细胞介素 1(IL 1)和LPS ;实验组 :SMT持续皮下注射 72h后 ,关节内注射同浓度IL 1β和LPS。经 8h后通过检测硝酸盐和亚硝酸盐的含量来观察膝关节滑液、滑膜和软骨NO的释放量以及iNOS的活性 ;用原位杂交检测软骨iNOSmRNA的表达。 48h后 ,通过Na2 3 5SO4 掺入法检测关节软骨蛋白多糖的合成率。结果　IL 1β和LPS混合液可诱发iNOSmRNA显著表达 ,使兔膝关节滑液、滑膜和软骨释放大量NO和增加NOS活性。关节软骨是关节内NO的主要来源。SMT减少了NO释放 ,降低了NOS活性 ,抑制了iNOSmRNA表达 ,并且部分逆转了蛋白多糖的抑制作用。结论　iNOS抑制剂SMT对关节软骨的损伤具有部分保护作用 ;Objective To study the effect of nitric oxide synthase inhibitors S methylisothiorurea (SMT) on cartilage metabolism after intraarticular injection of interleukin 1β (IL 1β) and lipopolysaccharides (LPS) in rabbits.Methods The experiments were performed in three groups:normal group,control group and SMT group.The effects of SMT on IL 1β and LPS induced iNOS mRNA expression ,NO production and NOS activity in synovium,synovial fluid and cartilage were detected after 8 h.Proteoglycan synthesis was measured by ex vivo incorporation of Na 2 35 SO 4 into cartilage after 48 h.Results IL 1β and LPS induced iNOS mRNA expression and increased NO release;SMT could reduce NO release and inhibit iNOS mRNA expression in synovium,synovial fluid and cartilage,and partly restore proteoglycan synthesis of cartilage.Conclusion iNOS inhibitor SMT can protect IL 1β and LPS induced cartilage damage in high concentration.

关 键 词：一氧化氮合酶 酶抑制剂 关节软骨 白细胞介素1Β 脂多糖类 

分 类 号：R684.3[医药卫生—骨科学]