巴戟天丸在骨质疏松性骨折愈合中的机制研究OA

Objective:To clarify the molecular mechanism by which Bajitian Pill intervenes in osteopo-rotic fractures,and to investigate the role of CD147-mediated macrophage regulation of osteoclast function in fracture repair.Methods:Fifty SPF-grade female SD rats were selected and randomly divided into the normal(N)group,the model(C)group,the low-dose Bajitian Pill(L)group,the medium-dose Bajitian Pill(M)group,and the high-dose Bajitian Pill(H)group,with 10 rats in each group.Group N was not subjec-ted to modeling,while the other four groups were ovariectomized and raised for 12 weeks to establish a bone osteoporosis model.Then,a mid-section fracture of the right femur was made and fixed with an intramedullary needle.The osteoporosis fracture modeling was completed.After successful modeling,group L,M,and H were given Bajitian Pill at concentrations of 0.4,0.8,and 1.2g/mL by gavage once a day for 8 consecutive weeks.Group N and group C were gavaged with the same volume of normal saline at the same time.The bone density and bone biomechanical properties of the rats were examined.Bone tissues were taken for HE staining and TRAP staining to detect the generation of osteoclasts.Serum macrophage-related factor levels were detec-ted by enzyme-linked immunosorbent assay,and the protein expressions of CD147,RANKL,and OPG in the bone tissues were detected by immunoblotting.Results:Compared with group N,the bone density,maximum load,elastic modulus,and fracture energy in group C decreased(P<0.05).Compared with group C,the maximum load,elastic modulus,and fracture energy in group L,M,and H increased(P<0.05),and the in-crease in group M was more significant than that in group L(P<0.05),and the increase in group H was more significant than that in group M(P<0.05).The bone trabeculae in group N were arranged regularly and densely,with a complete structure and uniform bone matrix,without obvious gaps.In group C,the bone cal-lus tissue had sparse and disordered bone trabeculae.The pathological morphology of bone tissue in group L,M,and H improved significantly compared with group C.Compared with group N,the number of osteoclasts in group C increased(P<0.05),and the number of osteoclasts in group L,M,and H decreased(P<0.05),and the decrease was more significant in group M than in group L(P<0.05),and in group H than in group M(P<0.05).Compared with group N,the levels of serum TNF-α and IL-6 in group C increased(P<0.05),and the levels of IL-10 and TGF-β decreased(P<0.05).Compared with group C,the levels of TNF-α and IL-6 in group L,M,and H decreased(P<0.05),and the levels of IL-10 and TGF-β increased(P<0.05),and the changes were more significant in group M than in group L(P<0.05),and in group H than in group M(P<0.05).Compared with group N,the protein expressions of CD147 and RANKL in group C in-creased(P<0.05),and the protein expression of OPG decreased(P<0.05).Compared with group C,the protein expressions of CD147 and RANKL in group L,M,and H decreased(P<0.05),and the protein ex-pression of OPG increased(P<0.05),and the changes were more significant in group M than in group L(P<0.05),and in group H than in group M(P<0.05).Pearson correlation analysis showed that CD147 was significantly positively correlated with TNF-α,IL-6,and the number of osteoclasts,and significantly nega-tively correlated with IL-10 and TGF-β.The number of osteoclasts was significantly positively correlated with TNF-α and IL-6,and significantly negatively correlated with IL-10 and TGF-β.Conclusions:Bajitian Pills can effectively promote bone healing in osteoporotic fracture rats.The mechanism of action may be to down-regulate the expression of CD147 to regulate the activity of macrophages,thereby inhibiting the exces-sive activation and differentiation of osteoclasts,ultimately slowing down bone resorption and promoting bone repair.