重组人中期因子midkine对大鼠膝关节软骨部分损伤的修复作用

目的:通过外源注射不同剂量的重组人中期因子midkine(rhMK),研究其对大鼠膝关节软骨部分损伤的修复作用。方法:雄性SD大鼠双侧膝关节建立软骨部分损伤的动物模型,术后24小时分别向关节腔内注射生理盐水或rhMK (20μg/kg、60μg/kg、180μg/kg)。于术后8周将大鼠全部处死,取材进行组织学观察,从而确定最佳注射剂量;在药代动力学研究中,按最佳注射剂量向正常大鼠膝关节腔内注射rhMK,分别于注射后1小时、1天、3天、6天、9天、12天和15天处死大鼠,检测膝关节软骨组织中rhMK的含量。结果:不同剂量的重组蛋白对膝关节软骨部分损伤均有不同程度的修复作用,其中180μg/kg的剂量效果最佳;以180μg/kg的剂量向正常大鼠膝关节腔内注射rhMK后,经过Kinetica5.0药代动力学软件拟合后,计算得rhMK在软骨组织中的消除相半衰期为8.69天。结论:rhMK对大鼠膝关节软骨部分损伤有明显的修复作用,最佳注射剂量为180μg/kg,最佳注射时间间隔为8天。

Recombinant Human Midkine Promotes the Repair of Partial Thickness Defects of Articular Cartilage in Rats

Objective:To study the role of recombinant human midkine (rhMK) in the repair of acute partial-thickness defects of knee articular cartilage. Methods:The animal model of acute partial-thickness defects in rats was constructed, then normal saline or rhMK (20μg/kg、60μg/kg、180μg/kg)was injected into knee cavity 24 hours after surgery.All rats were sacrificed on the 8th week after surgery, knee joints were taken to make paraffin sections, then sections were stained with Toluidine blue and observed with microscope to determine optimum dose of injection.Results:Different dose of rhMK could repair partial-thickness defects in different degree, the optimum dose of injection was 180μg/kg. For pharmacokinetic analysis, cartilage was harvested at 1 hour and 1, 3, 6, 9, 12 and 15 days after knee injection of 180μg/kg rhMK (n=4), the concentration of rhMK in cartilage tissue firstly increased and then decreased, the terminal T_1/2 in cartilage tissue was 8.69 days.Conclusion: rhMK could repair partial-thickness defects of knee articular cartilage in rats obviously, the optimum dose was 180μg/kg and the optimum interval of time was 8 days.