甘姜苓术汤对兔膝骨关节炎模型关节液中TGF-β_(1)和MMP-3表达水平的影响

Effect of Ganjiang Lingzhu Decoction(甘姜苓术汤) on the Expression Levels of TGF-β_(1) and MMP-3 in Synovial Fluid of Rabbit Knee Osteoarthritis Model

目的观察甘姜苓术汤对兔膝骨关节炎(knee osteoarthritis,KOA)模型转化生长因子-β_(1)(TGF-β_(1))和基质金属蛋白酶-3(MMP-3)表达水平的影响。方法选用日本大耳白兔24只,随机分成空白组、模型组、甘姜苓术汤组和双氯芬酸钠组4组,每组6只。空白组不做处理,模型组、甘姜苓术汤组及双氯芬酸钠组采用改良Hulth对兔左后膝关节制备兔KOA模型,治疗4周后测定各组兔膝关节液中的TGF-β_(1)和MMP-3水平,同时对滑膜、软骨组织进行形态学观察,评估兔干预前后行为学的改变。结果甘姜苓术汤能显著改善实验动物的行为学评分。此外,与模型组相比,甘姜苓术汤组和双氯芬酸钠组表层软骨剥脱较少,簇集表现不明显,细胞核变性较轻微,且甘姜苓术汤组的改善程度略优于双氯芬酸钠组。与空白组相比,其余3组兔膝关节液中MMP-3和TGF-β_(1)表达水平均上升,差异有统计学意义(P<0.05);与双氯芬酸钠组相比,甘姜苓术汤组兔膝关节液中MMP-3和TGF-β_(1)表达水平均下降,差异有统计学意义(P<0.05)。结论甘姜苓术汤对兔膝关节软骨损伤有治疗作用的机制与其可降低膝关节液中MMP-3和TGF-β_(1)两个指标的表达水平密切相关。

Objective To observe the effects of Ganjiang Lingzhu Decoction(甘姜苓术汤,GJLZ)on the expression levels of transforming growth factor-β1(TGF-β1)and matrix metalloproteinase-3(MMP-3)in rabbit knee osteoarthritis(KOA)model.Methods A total of 24 Japanese white rabbits were randomly divided into four groups:blank group,model group,GJLZ group and diclofenac sodium group.After four weeks of treatment,the levels of TGF-β1 and MMP-3 in the knee synovial fluid of each group were measured,the synovium and cartilage were morphologically observed,and the behavioral changes of rabbits before and after intervention were evaluated.Results GJLZ Decoction can significantly improve the behavior score of experimental animals.In addition,compared with the model group,GJLZ Decoction group and diclofenac sodium group had less surface cartilage exfoliation,less clustering,and less nuclear degeneration,and the improvement degree of GJLZ Decoction group was better than that of diclofenac sodium group.Compared with the blank group,the expression levels of MMP-3 and TGF-β1 in the knee synovial fluid of the other three groups increased,and the difference was statistically significant(P<0.05);Compared with the diclofenac sodium group,the expression levels of MMP-3 and TGF-β1 in the knee synovial fluid of rabbits in the GJLZ group were significantly decreased,and the difference was statistically significant(P<0.05).Conclusion The mechanism of GJLZ Decoction on rabbit knee joint cartilage injury is closely related to lowering the expression level of two indexes of MMP-3 and TGF-β1 in knee joint fluid.