Benton H P, Vasseur P B, Broderick-Villa G A, Koolpe M
Department of Anatomy, School of Veterinary Medicine, University of California, Davis 95616, USA.
Am J Vet Res. 1997 Mar;58(3):286-92.
To determine whether the nonsteroidal anti-inflammatory drug carprofen directly influences canine chondrocyte metabolism.
Cartilage from the femoral heads of 13 dogs undergoing total hip replacement.
Rates of glycosaminoglycan (GAG) synthesis and degradation, protein synthesis, cell viability, and prostaglandin release were determined in canine explant cartilage or monolayer canine chondrocyte cultures in the presence of 0 to 100 micrograms of carprofen/ml. Rate of GAG synthesis was assessed as incorporation of [35S]sulfate into cartilage matrix during a 3-hour pulse label. Degradation of cartilage GAG was assessed as rate of release of [35S]sulfate from prelabeled explant cultures. Rates of total protein synthesis were assessed as incorporation of [35S]methionine into trichloracetic acid precipitable material during a 3-hour pulse label. Radiolabeled chondrocyte proteins were separated by polyacrylamide gel electrophoresis and visualized by fluorography. Rates of prostaglandin E2 release were assessed by radioimmunoassay.
Carprofen stimulated a significant increase in the rate of GAG synthesis at concentrations of 1 and 10 micrograms/ml, with no change in total protein synthesis, pattern of new protein synthesis, or cell viability. At concentration > or = 20 micrograms/ml, inhibition of GAG synthesis and total protein synthesis was observed. There was no significant change in rate of release of GAG from cartilage explants, but potent inhibition of prostaglandin release was observed.
Carprofen has a direct influence on chondrocyte activity, resulting in changes in rate of production of cartilage matrix.
In determining the optimal therapeutic dose of carprofen for arthritic conditions in dogs, it is important to consider potential influences on cartilage, as well as anti-inflammatory actions.
确定非甾体抗炎药卡洛芬是否直接影响犬软骨细胞代谢。
13只接受全髋关节置换术的犬的股骨头软骨。
在含有0至100微克/毫升卡洛芬的情况下，测定犬外植体软骨或单层犬软骨细胞培养物中糖胺聚糖（GAG）合成和降解速率、蛋白质合成、细胞活力以及前列腺素释放。GAG合成速率通过在3小时脉冲标记期间[35S]硫酸盐掺入软骨基质来评估。软骨GAG的降解通过预标记外植体培养物中[35S]硫酸盐的释放速率来评估。总蛋白质合成速率通过在3小时脉冲标记期间[35S]甲硫氨酸掺入三氯乙酸可沉淀物质来评估。放射性标记的软骨细胞蛋白质通过聚丙烯酰胺凝胶电泳分离并通过荧光显影可视化。前列腺素E2释放速率通过放射免疫测定法评估。
卡洛芬在浓度为1和10微克/毫升时刺激GAG合成速率显著增加，总蛋白质合成、新蛋白质合成模式或细胞活力无变化。在浓度≥20微克/毫升时，观察到GAG合成和总蛋白质合成受到抑制。软骨外植体中GAG释放速率无显著变化，但观察到前列腺素释放受到有效抑制。
卡洛芬对软骨细胞活性有直接影响，导致软骨基质产生速率发生变化。
在确定犬关节炎疾病中卡洛芬的最佳治疗剂量时，重要的是要考虑对软骨的潜在影响以及抗炎作用。
