Mechanism of Guigui Zhuanggu Tablet on the Treatment of Knee Osteoarthritis
Objective:To investigate the mechanism of Guigui Zhuanggu tablet(GZT)on the treatment of knee osteoar-thritis(KOA)in rat models and chondrocytes.Methods:After adapting for 1 week,64 male SD rats were randomly divided into the sham group,model group,Glucosamine Sul-fate capsule(GSC)group,and GZT group according to the surgical sequence at treated days 28 and 56.Each group consisted of 8 rats.Except for the sham group and model group were treated with normal saline by intragastric administration,the other groups were given GSC and GZT solution.The medial meniscus transection(MMT)was used to induce KOA in the right knee joint of the rats,and the successful model-ing was confirmed by the clear separation of the rat's medial meniscus during the surgery.Each group of rats was subjec-ted to foot mechanical pain threshold assessment before and after modeling at 0,7,14,21,28,35,42,49 and 56 d.The con-centration of IL-1β and TNF-a in the joint lavage fluid and MMP-13 and ADAMTS-5 protein expression level in the tibial plateau cartilage were detected after 28 d and 56 d of modeling.The pathological changes in the coronal plane of the rat's knee joint were also observed.The study observed the effects of GZT-containing rabbit serum with different concentrations and treatment durations on the viability of primary chondrocytes from 12 SD rat pups,using normal serum and drug-containing serum from 10 male New Zealand rabbits.Results:The mechanical pain thresholds of rats in the model group were significantly lower than those in the sham group,with a statistically significant difference(P＜0.01).Compared with the overall effect in the model group,the mechanical pain thresholds of rats in the GZT group were significantly higher,with a statistically significant difference(P＜0.001).The concentrations of IL-1β and TNF-α in the joint lavage fluid of rats in the GZT group did not differ significantly from those in the model group(P＞0.05),only at 28 d,the concentration of IL-1β in the joint lavage fluid of rats in the GZT group was significantly reduced compared to that in the model group,with a statistically significant difference(P＜0.01).Compared with the model group,most of the surface of the knee joint cartilage in the GZT group rats was smooth and orderly,with irregularities in some parts of the cartilage,diffuse increase in chon-drocytes,and fibrotic changes in some bone marrow stromal cells,however,the osteophyte was significantly thickened.The OARSI total joint scores in the GZT group rats were significantly lower than that in the model group after intervention,with a statistically significant difference(P＜0.05).There was no significant difference in the expression levels of MMP-13 and ADAMTS-5 in the tibial plateau cartilage of GZT group rats at 28 d compared to those in the model group(P＞0.05).The expression levels of MMP-13 and ADAMTS-5 in the tibial plateau cartilage of GZT group rats at 56 d were significantly reduced,with a statistically significant difference(P＜0.05).The GZT-containing serum could promote the viability of primary chondrocytes(P＜0.01),showing temporal but not concentration-dependent characteristics.Conclusion:GZT can protect joint cartilage by inhibiting the expression of MMP-13 and ADAMTS-5 and promoting the vitality of chondrocytes,thus reducing cartilage degeneration induced by MMT surgery.Furthermore,GZT can increase the mechanical pain threshold of rats with knee osteoarthritis.
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