Effect of Evodiamine on Macrophage Polarization in Knee Osteoarthritis by Regulating NF-κB Pathway
Objective To explore the effect of evodiamine(EV)on macrophage polarization in knee osteoarthritis(OA)rats by regulating the nuclear transcription factor-κB(NF-κB)pathway.Methods SD rats were used to establish a knee osteoarthritis model by intra-articular injection of sodium iodoacetate(MIA).They were randomly separated into model group,low-dose(6.9 mg/kg)EV group,high-dose(13.8 mg/kg)EV group,high-dose(13.8 mg/kg)EV+phorbol 12-myristate 13-acetate(PMA)(2μg/kg)group,with 10 rats in each group.Ten rats were selected as the control group,and an equal amount of normal saline was injected into the joint cavity of each rat.After EV and PMA treatment,the joint tenderness threshold,joint swelling rate,joint range of motion,and gait score of rats were measured in each group.The pathological morphology of cartilage and synovial tis-sues of rats in each group was detected by safranin O-fixed green and HE staining.Macrophage polarization in synovial tissue of rats in each group was detected by flow cytometry.The levels of pro-inflammatory factors[interleukin-6(IL-6),IL-1,and IL-1β]in the serum and synovial fluid of rats in each group were detected by ELISA.The expression levels of NF-κB pathway related proteins in rat articular cartilage and synovial tissue were detected by Western blotting.Results Compared with the control group,pathological damage of the cartilage and synovial tissue morphology in rats in the model group was more obvious,the threshold for joint tenderness and joint range of motion were reduced significantly(all P＜0.05).The joint swelling rate,synovi-al thickness,gait score,cartilage pathology score,synovial pathology score,proportion of M1 macrophages and M1/M2 ratio in synovial tissue,the levels of IL-6,IL-1,IL-1β in serum and synovial fluid,p-inhibitor of NF-κBa(p-IκB-a)/IκB-a,p-NF-κB p65/NF-κB p65 in cartilage and synovial tissue were increased significantly(all P＜0.05).Compared with the model group,the mor-phological and pathological damage to the cartilage and synovial tissues of rats in the low-dose and high-dose EV groups was re-duced,the joint range of motion and the proportion of M2 macrophages in synovial tissue were increased(all P＜0.05).The joint swelling rate,synovial thickness,gait score,cartilage pathology score,synovial pathology score,proportion of M1 macro-phages and M1/M2 ratio in synovial tissue,the levels of IL-6,IL-1,IL-1β in serum and synovial fluid,p-IκB-α/IκB-α,p-NF-κB p65/NF-κB p65 in cartilage and synovial tissue were reduced(all P＜0.05).Effect of EV increased with increasing concentra-tion.Effects of EV was inhibited in terms of the above indicators in OA rats after PMA treatment.Conclusion EV can promote polarization of M2 macrophages and inhibit polarization of M1 macrophages by blocking NF-κB signaling pathway activation,thereby reducing inflammation in knee osteoarthritis rats and improving symptoms such as joint pain,swelling,and limited mob-ility.
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维普
