跌打通痹膏对兔膝骨关节炎退变关节软骨细胞MMP-1、MMP-3表达的影响

Impacts of Dieda Tongbi Ointment on MMP-1 and MMP-3 Expressions of the Chondrocytes in the Rabbits of Knee Osteoarthritis

目的观察跌打通痹膏对兔膝骨关节炎模型关节液中MMP-1、MMP-3表达的影响,研究跌打通痹膏治疗膝骨关节炎的作用机制,为跌打通痹膏临床应用的推广提供实验与理论依据。方法随机将61只月龄8月、体重1.5~2.5 kg健康新西兰大白兔分成空白组、假手术组、模型组、跌打通痹膏组、骨通贴组,每组12只,另1只为改良型Hulth造模法造模后的模型验证兔。空白组不做任何处理,模型组、跌打痛痹膏组、骨通贴组采用改良型Hulth造模法,假手术组打开关节腔后直接缝合。术后第5周造模验证成功后,进入实验处理部分。空白组、假手术组不予治疗,模型组用普通医用胶带固定,跌打通痹膏组用跌打通痹膏贴敷,骨通贴组用骨通贴膏贴敷。胶带、跌打通痹膏、骨通贴膏经计算后均裁剪为2 cm×4 cm大小,固定于右膝关节,按照使用说明每日1次,每日8 h后取掉,连续4周。第5周后观察实验兔行为变化、X线下关节软骨改变情况,检测关节软骨中MMP-1、MMP-3的表达。结果全部实验兔均成活至观察时间且无一出现过敏现象;右膝关节X线正侧位提示跌打通痹膏组、骨通贴组两组经治疗后较模型组改善。关节软骨观察:1肉眼观察评分:跌打通痹膏组、骨通贴组评分较模型组低(P<0.05)。2光镜下关节软骨评分:跌打通痹膏组、骨通贴组评分较模型组低(P<0.05)。MMP-1、MMP-3检测:模型组、跌打通痹膏组、骨通贴组与空白组比较,MMP-1、MMP-3表达显著提高(P<0.01),跌打通痹膏组、骨通贴组与模型组比较,MMP-1、MMP-3表达降低(P<0.01)。结论通过改良型Hulth造模法可成功复制兔KOA模型,跌打通痹膏和骨通贴对KOA均有治疗作用,可延缓KOA的病程,但不能治愈KOA。

Objective To observe the impacts of dieda tongbi ointment on MMP- 1 and MMP- 3expressions of synovial fluid in the rabbit model of knee osteoarthritis( KOA) and explore its action mechanisms on the treatment so as to provide the experimental support and theoretical evidence for the clinical application. Methods Sixty- one healthy New Zealand purebred- rabbits,8 months old,1. 5 ~ 2. 5 kg were randomly divided into blank group,sham- operation group,model group,Dieda Tongbi ointment group and a Gutong plaster group,12 rabbits in each one; and the other one was prepared as the model validation after the modified Hulth modeling. No treatment was used in the blank group. The modified Hulth modeling method was applied in the rest group except in the sham- operation group. The joint cavity was sutured directly after opening in the sham- operation group. The experimental treatment was followed after the success of model validation in 5 weeks of operation. No any treatment was provided in the blank group and the sham- operation group. In the model group,the common medical tape was used for fixation. In the Dieda Tongbi ointment group,the Dieda Tongbi ointment plaster was used. In the Gutong plaster group,Gutong plaster was used. The size of tape and plasters was 2 cm × 4 cm. They were fixed on the right knee,one day at a time,removedafter 8 hours,applying for 4 weeks. Five weeks later,the rabbit behavior,X- ray changes and the changes of joint cartilage were observed. MMP- 1 and MMP- 3 expressions were detected in the joint cartilage. Results All of the experimental rabbits were survived till the observation time,without any allergic reaction happening. The lateral film conditions of X- ray of the right knee joint in the Dieda Tonggu ointment group and the Gutong plaster group were improved as compared with the model group after treatment. Observation of articular cartilage: Visual study showed that the scores in the two plaster groups were lower than those in the model group( P < 0. 05). The electron microscopic study showed that the scores in the two plaster groups were lower than those in the model group( P < 0. 05). MMP- 1 and MMP- 3 test: MMP- 1 and MMP- 3 expressions in the two plaster groups were improved significantly as compared with the blank group( P < 0. 01),and were reduced as compared with the model group( P < 0. 01). Conclusion Rabbit KOA models are successfully duplicated with modified Hulth modeling method. Dieda Tongbi ointment and Gutong plaster bring the therapeutic effect on KOA,delay the progress of disease. However,they cannot cure KOA.