Muir H, Carney S L, Hall L G
Biochemistry Division, Kennedy Institute of Rheumatology, London.
Drugs. 1988;35 Suppl 1:15-23. doi: 10.2165/00003495-198800351-00006.
Using in vitro methods, we have determined the effects of four NSAIDs on the biosynthesis and turnover of proteoglycans in articular cartilage explants. Over the concentration ranges examined (5 X 10(-7) to 10(-5) mol/L for tiaprofenic acid, naproxen and indomethacin; 5 X 10(-5) to 10(-3) mol/L for aspirin), all the drugs examined, except tiaprofenic acid, reduced the rate of proteoglycan synthesis compared with control tissue. All of the compounds examined reduced the turnover rate of newly synthesised proteoglycans. The products of turnover of explants treated with the various NSAIDs did not appear to be significantly different from those produced by control tissue, as assessed by gel chromatography and electrophoresis. There were some indications, however, of quantitative differences in distribution on both these analytical systems. These results indicate that with the exception of tiaprofenic acid all the NSAIDs examined produced a general reduction in chondrocyte metabolic activity. Thus it seems unlikely that tiaprofenic acid would have a direct detrimental effect on articular cartilage during long term administration.
我们采用体外实验方法,测定了四种非甾体抗炎药(NSAIDs)对关节软骨外植体中蛋白聚糖生物合成及更新的影响。在所检测的浓度范围内(噻洛芬酸、萘普生和吲哚美辛为5×10⁻⁷至10⁻⁵mol/L;阿司匹林为5×10⁻⁵至10⁻³mol/L),除噻洛芬酸外,所有检测药物与对照组织相比均降低了蛋白聚糖的合成速率。所有检测的化合物均降低了新合成蛋白聚糖的更新速率。通过凝胶色谱法和电泳评估,用不同NSAIDs处理的外植体更新产物与对照组织产生的产物似乎没有显著差异。然而,在这两种分析系统上的分布存在一些定量差异的迹象。这些结果表明,除噻洛芬酸外,所有检测的NSAIDs均使软骨细胞代谢活性普遍降低。因此,长期给药期间噻洛芬酸似乎不太可能对关节软骨产生直接有害影响。