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关键词： 一氧化氮(NO),软骨破坏
一氧化氮(NO)在不同的生物系统中充当调节和效应因子〔1～5〕，如作为神经递质在神经系统中发挥作用，松驰平滑肌，抑制血小板聚集，介导细胞增殖抑制和非特异抗微生物防御反应。近来研究发现NO参与软骨破坏的病理过程。
NO由一氧化氮合酶(NOS)催化L-精氨酸产生，需要烟酰胺腺嘌呤二核苷酸(NAPDH)、四氢叶酸和分子氧作为辅助因子〔6〕。新生成的NO在局部激活鸟苷酸环化酶，升高细胞内cGMP水平，发挥生物学效应〔7〕。NOS按表达方式分为自发型(包括神经型和内皮型)和诱导型(iNOS)两种，两种酶在多种细胞中共同存在，但相对水平不同。自发型需要Ca2+/Ca2+通道参与〔8〕，蛋白激酶C(PKC)、cAMP依赖蛋白激酶(PKA)等通过磷酸化NOS调节其活性〔9〕。自发型仅产生少量NO。而诱导型在细胞因子如白细胞介素-1(IL-1)、肿瘤坏死因子(TNF)等和脂多糖(LPS)刺激数小时后即产生大量NO，其活性依赖于mRNA的产生和蛋白表达，与Ca2+/Ca2+通道无关。iNOS在不同细胞中的质和量不同，在人肝细胞中NO的诱导需要IL-1、TNF、LPS和干扰素(IFN)联合刺激，而IL-1单独刺激血管平滑肌细胞产生NO。软骨细胞在IL-1、LPS和TNF单独刺激下产生大量NO，作用具有协同性〔10〕。
编码人软骨细胞iNOS的cDNA已被克隆，是一条4.5kb的单链，编码一条1153个氨基酸序列的长链蛋白〔11〕。与鼠巨噬细胞iNOS相比，cDNA具有78%同源性，蛋白质具有88%同源性。与鼠巨噬细胞NOS相比，同源性较低。iNOS和NOS都有黄素腺嘌呤二核苷酸(FAD)、黄素单核苷酸(FMN)、NAPDH和钙通道结合位点。糖皮质激素和非甾体抗炎药在其他细胞能抑制iNOS的表达，但对软骨细胞iNOS的表达无影响〔12〕。有资料报道软骨细胞内Ca2+浓度升高可减少iNOS mRNA的稳定性，软骨细胞iNOS是一种钙依赖的新型合酶〔13〕。PKC、PKA等与软骨细胞iNOS活性无关，而酪氨酸激酶(PTK)激活可以促进软骨细胞iNOS mRNA产生和蛋白表达〔14〕。
目录：
1 NO抑制软骨细胞增殖，诱导软骨细胞凋亡
2 NO对蛋白聚糖(PG)代谢的影响
3 NO促进MMPs的产生
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