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一氧化氮与软骨损伤
IL-1刺激兔软骨细胞引起92KD(MMP-9)和72KD(MMP-2)酶活性增加，其中MMP-9活性在12 h即可检测出来，L-NMMA可以抑制IL-1的这种作用。SPN剂量依赖性地促进MMP-9的活性〔23〕。NO促进MMP-9活性发生在转录水平。IL-1刺激兔软骨细胞产生大量NO，NO促进MMP-9和碱性成纤维细胞生长因子(bFGF) mRNA产生，而bFGF反过来又促进MMP-9 mRNA产生，bFGF与IL-1在同等程度上促进产生，而且有协同作用。bFGF与IL-1通过不同途径促进MMP-9 mRNA产生。IL-1促进MMP-9和bFGF mRNA产生是由NO介导的。L-NMMA除了直接抑制IL-1刺激MMP-9产生外，还可以通过抑制bFGF间接抑制MMP-9产生〔24〕。
RA的病因迄今未明，给临床治疗工作带来难题。目前用于RA治疗的药物主要是免疫抑制剂，如抗代谢药、糖皮质激素，但临床效果并不理想，而且这些药物对全身免疫系统都有抑制作用。由于NO可以从以上几个方面破坏软骨，且是RA软骨细胞自分泌或旁分泌产生，能从局部作用于全身，所以从NO角度治疗RA有望成为一种新的治疗途径。目前NOS抑制剂在关节炎动物模型实验中取得了较好疗效〔19〕，但临床实验效果并不佳。这除了RA病理因素复杂、作用环节较多外，还可能与给药途径有关。多环节抑制剂的联合用药已经取得良好效果，所以包括抑制NO产生药物在内的作用与多环节的联合用药可能有一定的临床应用前景。
作者单位：第三军医大学新桥医院(重庆，400037)
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