一侧兔膝关节注射外源性尿激酶型纤溶酶原激活物引起双侧膝关节软骨降解的实验

Cartilage degeneration of bilateral knee joint induced by unilateral articular injection of exogenous urokinase-type plasminogen activator in rabbits

目的:观察关节腔内注射外源性尿激酶型纤溶酶原激活物对关节软骨的影响。方法:实验于2005-01/2006-06在新疆石河子大学动物实验中心完成。将48只大白兔按体质量、性别随机分为实验组(n=24)、空白对照4周组(n=6)、盐水对照组(n=18)。实验组每只兔子在右膝关节内注射外源性尿激酶型纤溶酶原激活物0.2mL(0.4μg);空白对照4周组,未行任何处理;盐水对照组在右膝关节内注射生理盐水0.2mL。造模后4,8,12周分批麻醉处死后取兔双膝关节软骨进行组织学观察及电镜检查。结果:纳入大白兔48只,均进入结果分析,实验过程中无1例膝关节感染发生。①实验组兔双膝关节软骨表面不规则、缺损及结构破坏,软骨细胞数目明显减少、纤维增生,并出现潮线的完整性破坏。②Mankin’s评分结果显示,盐水对照组与空白对照4周组之间比较,软骨没有任何变化(0.83±0.75,0.80±0.74,P>0.05),而与实验组之间比较,不论4,8,12周,差异均有显著性意义(0.83±0.75,5.38±0.92;1.00±0.63,8.25±1.39;0.83±0.75,11.75±0.89;P<0.01),同时实验组各时间点之间比较,差异也有显著性意义(5.38±0.92,5.35±0.90;8.25±1.39,8.51±0.94;11.75±0.89,12.03±0.91;P<0.05)。结论:①实验结果显示,兔双膝关节均出现关节软骨损伤的病理现象。②尿激酶型纤溶酶原激活物可能是关节软骨降解的始动因子,对软骨的降解起着重要的病理作用,促使软骨降解病变的逐步加重。

AIM： To observe the effects of intra-articular injection of exogenous urokinase-type plasminogen activator （UPA） on cartilage. METHODS： The experiment was conducted in the Animal Experiment Center, Xinjiang Shihezi University from January 2005 to June 2006. The 48 rabbits were divided into experimental group （n =24） and blank control 4-week group （n =6） and saline control group （n =18） according to body mass and the sex. Rabbits in the experimental group were injected intraarticularly with 0.4 μg/0.2 mL UPA. Animals in the blank control group did not receive any treatment. Animals in the saline control group received 0.2 mL saline in right knee joint. 4, 8 and 12 weeks after establishing models, the rabbits were respectively sacrificed to obtain cartilage of both knee joints for histology observation and electron microscopy. RESULTS： A total of 48 rabbits were involved in the result analysis, and no infection occurred during experiment. （1）The surface of the right and left kneel joint cartilage in experimental group showed irregularity, defection and structural breakage, the number of cartilage call reduced and collagen fiber hyperplasia and tide line of complete break. （2） Mankin＇s score showed that there was no change of cartilage in saline control group and blank control 4-week group （0.83±0.75,0.80±0.74, P 〉 0.05）. There were significant differences as compared with the experimental group at weeks 4, 8 and 12 （0.83±0.75,5.38±0.92; 1.00±0.63,8.25±1.39 ;0.83±0.75,11.75±0.89; P 〈 0.01 ）. At the same time, there were significant differences in the experimental group at different time points （5.38±0.92,5.35±0.90;8.25±1.39,8.51±0.94; 11.75±0.89,12.03±0.91 ;P 〈 0.05）. CONCLUSION： （1）Findings of the trial showed pathological phenomenon of cartilage injury appeared in both knee joints of rabbits. （2）UPA may be the initiation factor of cartilage degradation, and plays important pathological effects for degradation, and accelerates the severity of articular cartilage degradation.