喹诺酮类药物对离体兔软骨细胞的毒性

Chondrotoxicity of quinolones on cultured chondrocytes of rabbit

目的 :评价几种喹诺酮类药物对幼龄兔软骨细胞的相对毒性 ,软骨毒性与浓度、时间、年龄的关系。方法 :采用兔软骨细胞体外培养的技术 ,观察细胞形态 ,四氮甲基唑蓝 (MTT)法评价细胞的增殖 ,二甲基亚甲蓝 (DMB)法评价细胞蛋白多糖的含量。观察环丙沙星、左氧氟沙星、氟罗沙星、帕珠沙星对 1月龄兔软骨细胞的影响 ,及环丙沙星对 1,3,5月龄兔软骨细胞的影响。结果 :喹诺酮类药物使细胞形态发生改变 ;抑制细胞的增殖的作用依次为环丙沙星 >左氧氟沙星 >氟罗沙星 >帕珠沙星 ;对蛋白多糖含量的作用为环丙沙星 >左氧氟沙星 >氟罗沙星、帕珠沙星 ;环丙沙星的抑制作用随作用时间的延长和浓度的增加而增加 ,随兔年龄的增大而减少。结论 :喹诺酮类几种药物的软骨毒性存在着差异 ,且随浓度、时间、年龄不同而不同。

AIM: To evaluate the relation between the relative toxicity, chondrotoxicity of some kinds of quinolones on chondrocytes of younger rabbits and the concentration, animal age, treatment duration. METHODS: The chondrocytes were isolated from joint cartilage of 1-month old rabbits and the influences of ciprofloxacin, levofloxacin, fleroxacin, pazufloxacin, on chondrocytes of 1-month old rabbits and the influence of ciprofloxacin on chondrocytes of 1, 3, 5-month old rabbits were observed respectively. The proliferation and secretion of proteoglycan were determined with 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and 1,9-dimethylmethylene blue (DMB) assay. RESULTS: Morphologic changes occurred in cells cultivated with QNs. The order of inhibiting proliferation was ciprofloxacin>levofloxacin >fleroxacin>pazufloxacin and the order of the effect on content of proteoglycan was ciprofloxacin>levofloxacin>fleroxacin and pazufloxacin. The effect of ciprofloxacin became larger with the length of duration and the increase of concentration, while became less following the rabbits age. CONCLUSION: There are differences in the chondrotoxicity of some kinds of quinolenes and those are found to be time-, concentration-, age-dependant.