Williams R J, Attia E, Wickiewicz T L, Hannafin J A
Laboratory for Soft Tissue Research, Sports Medicine & Shoulder Service, Hospital for Special Surgery, New York, New York, USA.
Am J Sports Med. 2000 May-Jun;28(3):364-9. doi: 10.1177/03635465000280031401.
The pathologic mechanisms underlying fluoroquinolone-induced tendinopathy are poorly understood. The observed incidence of tendinitis and tendon rupture in patients treated with ciprofloxacin hydrochloride suggests that the fluoroquinolone antibiotics alter tendon fibroblast metabolism. The purpose of this study was to examine the effect of ciprofloxacin on fibroblast metabolism in vitro. Canine Achilles tendon, paratenon, and shoulder capsule specimens were maintained in culture with ciprofloxacin (5, 10, or 50 microg/ml). Fibroblast proliferation, collagen synthesis, proteoglycan synthesis, and matrix-degrading activity were analyzed. Incubation of Achilles tendon, Achilles paratenon, and shoulder capsule fibroblasts with ciprofloxacin resulted in a statistically significant 66% to 68% decrease in cell proliferation compared with control cells at day 3 in culture. Ciprofloxacin caused a statistically significant 36% to 48% decrease in collagen synthesis compared with controls in all fibroblast cultures. Ciprofloxacin caused a statistically significant 14% to 60% decrease in proteoglycan synthesis in all fibroblast cell lines. Compared with unstimulated control fibroblasts, culture media from Achilles tendon, paratenon, and shoulder capsule cells that were exposed to ciprofloxacin demonstrated statistically significant increases in matrix-degrading proteolytic activity after 72 hours in culture. This study demonstrates that ciprofloxacin stimulates matrix-degrading protease activity from fibroblasts and that it exerts an inhibitory effect on fibroblast metabolism. The increase in protease activity and the inhibition of both cell proliferation and the synthesis of matrix ground substance may contribute to the clinically described tendinopathies associated with ciprofloxacin therapy.
氟喹诺酮类药物诱发肌腱病的病理机制目前尚不清楚。盐酸环丙沙星治疗患者中观察到的肌腱炎和肌腱断裂发生率表明，氟喹诺酮类抗生素会改变肌腱成纤维细胞的代谢。本研究的目的是在体外研究环丙沙星对成纤维细胞代谢的影响。将犬跟腱、腱旁组织和肩袖标本与环丙沙星（5、10或50微克/毫升）一起进行培养。分析成纤维细胞增殖、胶原蛋白合成、蛋白聚糖合成和基质降解活性。在培养第3天，与对照细胞相比，环丙沙星孵育跟腱、跟腱腱旁组织和肩袖成纤维细胞导致细胞增殖统计学上显著降低66%至68%。在所有成纤维细胞培养物中，与对照相比，环丙沙星导致胶原蛋白合成统计学上显著降低36%至48%。在所有成纤维细胞系中，环丙沙星导致蛋白聚糖合成统计学上显著降低14%至60%。与未刺激的对照成纤维细胞相比，暴露于环丙沙星的跟腱、腱旁组织和肩袖细胞的培养基在培养72小时后显示出基质降解蛋白水解活性统计学上显著增加。本研究表明，环丙沙星刺激成纤维细胞的基质降解蛋白酶活性，并对成纤维细胞代谢产生抑制作用。蛋白酶活性的增加以及对细胞增殖和基质基础物质合成的抑制可能导致临床上描述的与环丙沙星治疗相关的肌腱病。
