LIGUSTRAZINE REDUCES CARTILAGE DESTRUCTION IN MODEL OF OSTEOARTHRITIS IN RATS

Objective To study the effect and possible mechanism of Ligustrazine-a chinese traditional herbal medicine (CTM) on rat osteoarthritis (OA). Methods OA model was surgically induced. Morphology of articular cartilage was done by HE staining and mankin score was calculated; interleukin-1 and TNFα activity of rat joints was determined by 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method; immunohistochemistry of MMP-13 and Cathepsin K was done by ABC method while the mRNA level for MMP-13, cathepsin K and tissue inhibitor of matrix metalloproteinase 1 (TIMP-1) was evaluated by RT-PCR method. ResultsLigustrazine (60 mg·kg-1·d-1 or 30 mg·kg-1·d-1, but not 10 mg·kg-1·d-1, im, ×8 weeks) reduced morphological changes of articular cartilage of OA rats. IL-1 and TNFα production of OA joints increases, together with MMP-13, cathepsine K and their mRNA levels in articular cartilage. The administration of Ligustrazine (60 mg·kg-1·d-1or 30 mg·kg-1·d-1, im, ×8 weeks) reduced above changes significantly. At the same time, tissue inhibitor of metrix metalloprotease (TIMP1) mRNA level increased also in OA rats while Ligustrazine (60 mg·kg-1·d-1, 30 mg·kg-1·d-1or 10 mg·kg-1·d-1, im, ×8 weeks) had no significant effect on it. Conclusion Ligustrazine (60 mg.kg-1 d-1 or 30 mg·kg-1·d-1, but not 10 mg·kg-1·d-1, im, ×8 weeks) effectively delays articular cartilage degradation of OA rats and could be a potential drug candidate for OA treatment.