一氧化氮抑制兔关节软骨细胞II型胶原的合成

Nitric Oxide Inhibits the Synthesis of Type Ⅱ Collagen in Rabbit Cultured Chondrocytes

一氧化氮 (NO)在骨关节炎和关节软骨代谢中具有重要的病理生理作用。为研究NO与关节软骨II型胶原的关系 ,我们在培养的兔关节软骨细胞中以药物刺激产生NO后 ,分别用ELISA及RT -PCR法测定II型胶原及前II型胶原α1链 (COL2A1)mRNA表达量的变化。结果表明 ,0 2mM的硝普钠 (SNP)可释放出大量NO ,使软骨细胞II型胶原的含量减低 ,同时 ,RT -PCR法证实前II型胶原mRNA表达量也减少。 10 0u/ml白细胞介素 - 1(IL - 1)可刺激软骨细胞释放NO并使II型胶原量降低 ,其COL2A1mRNA表达量也减少。加用 1mg/ml精氨酸甲酯 (NAME ,NO合酶抑制剂 )后 ,则抑制了IL - 1的作用 ,使NO产量下降 ,II型胶原含量部分恢复 ,COL2A1完全恢复。本试验证实了NO作为IL - 1的下游分子抑制II型胶原的合成 ;其抑制作用是通过减少前II型胶原α1链mRNA表达量完成的。

Nitric oxide (NO) plays an important pathophysiological role in osteoarthritis and cartilage metabolism To determine the relationship between NO and the synthesis of type II collagen in cartilage, we measured levels of type II collagen by ELISA and procollagen (II) mRNA by RT-PCR in cultured lapine chondrocytes that were incubated with some kinds of reagents 0 2mM sodium nitroprusside (SNP, a NO donor) can release high levels of NO, decreasing type II collagen, suppressing the expression of procollagen (II) mRNA (COL2A1) At the same time, chondrocytes showed a large increase in NO synthesis, a decrease in type II collagen and COL2A1 mRNA in response to 100u/ml IL-1 When 1mg/ml N-nitro-L-arginine methyl easter (NAME, an inhibitor of NO synthase) was mixed with IL-1, NO production was inhibited, the amounts of type II collagen recovered partially and COL2A1 mRNA recovered completely These data indicate NO can inhibit type II collagen synthesis as IL-1 downstream molecule by suppressing procollagen (II) mRNA