新生大鼠血清和关节软骨喹诺酮类药物浓度与关节软骨细胞外基质变化的相关性研究

目的 探讨喹诺酮类药物对新生大鼠关节软骨的损伤作用及其损伤机制.方法 将60只日龄2天的新生大鼠随机分为对照组、小剂量组和大剂量组各20只,每组又根据处死动物的时间随机分为7天、14天两个亚组,每个亚组10只.对照组不注射任何药物,小剂量组、大剂量组自实验开始第1天腹腔分别注射左氧氟沙星（商品名：左克）10 mg/（kg＆#183;d）、20 mg/（kg＆#183;d）,每天1次,连用7天.各组动物分别在实验第7、14天取血清及关节软骨组织标本,采用高效液相色谱法测定血清、关节软骨左氧氟沙星药物浓度;采用酶联免疫吸附法（ELISA）测定血清Ⅱ型胶原（COLⅡ）、Ⅰ型前胶原羧基端前肽（PICP）及金属蛋白酶-3（MMP-3）水平.结果 7天时对照组血清和关节软骨组织中均未检测出左氧氟沙星,小剂量组血清和关节软骨组织左氧氟沙星含量均低于大剂量组血清：（0.99＆#177;0.33） mg/L比（2.22＆#177;0.96） mg/L,关节软骨：（0.77＆#177;0.30）tμg/g比（1.82＆#177;0.30） μg/g,P均＜0.01];14天时各组血清和关节软骨组织均未检测出左氧氟沙星.血清、关节软骨左氧氟沙星药物浓度与血清COLII含量呈负相关（P＜0.05）,与血清PICP、MMP-3含量无相关性（P＞0.05）.结论 血清和关节软骨组织喹诺酮类药物浓度与血清COLII含量呈负相关,血清和软骨组织高浓度喹诺酮类药物对新生大鼠关节软骨有明显损伤作用.

The relationship of quinolone concentration in serum and articular cartilage and changes of articular cartilage extracellular matrix in newborn rats

Objective To investigate the effects and mechanisms of quinolones （QNS） on articular cartilage in newborn rats. Methods Total of 60 newborn rats aged 2-day were proportionally assigned into 3 groups： Group Ⅰ： normal control group receiving no intervention. Group Ⅱ receiving intraperitoneal injection of lower doses of QNS 10 mg/（kg, d）1 each day for 7 days, and Group m higher doses 20 mg/（ kg. d） ]. Each group were subsequently divided into two subgroups based on the time they were executed （7-day and 14-day subgroup） , with 10 rats in each subgroup. On the 7th day and the 14th day of the experiment, concentration of QNS in serum and articular cartilage were examined using high performance liquid chromatography. Type Ⅱ collagen （COL Ⅱ ）, type I procollagen （PICP） and matrix etalloproteinases-3 （MMP-3） in serum were examined using enzyme-linked immunosorbent assay （ELISA） . Results On the 7th day, QNS in serum and articular cartilage in Group Ⅱ are （0. 99 ± 0. 33 ） mg/L and （0. 77 ± 0.30 ） p~g/g respectively, and （2.22 ± 0. 96 ） mg/L and （ 1.82 ± 0. 30） μg/g in Group HI. However on the 14th day, no QNS was detected in serum and articular cartilage in all groups. QNS in serum and articular cartilage and COL I1 in serum are negatively correlated （P 〈 0. 05 ）, no correlation as to serum PICP and MMP-3 （ P 〉 0. 05 ）. Conclusions High doses of QNS cause damage to the articular cartilage in newborn rats.