Effect of shikonin on inflammatory response in rats with knee osteoarthritis by regulating NF-κB/ERK signaling pathway / 中国免疫学杂志

ABSTRACT

Objective:Constructing a rat model of knee osteoarthritis,to explore effects of shikonin on inflammatory response,NF-κB/extracellular regulated protein kinase(ERK)pathway in knee osteoarthritis rats,and the possibility of NF-κB/ERK signaling pathway as a new target for shikonin.Methods:Seventy-two male SD rats were collected,and randomly separated into sham operation group,arthritis group,nimesulide group,shikonin group,shikonin+ERK activation group and shikonin+NF-κB activation group,with 12 rats per group.A rat model of knee osteoarthritis was constructed,and the arthritis indexes of rats in each group were evaluated to judge the model construction;safranin fast green staining and HE staining were performed to observe the pathology of knee cartilage of rats in each group;ELISA was performed to measure levels of IL-1β,IL-6 and TNF-α in serum and cartilage tissue of rats in each group;Western blot was performed to measure NF-κB p65,ERK,p-NF-κB p65 and p-ERK protein expressions in cartilage tissue.Results:Cartilage tissue of rats in sham operation group had no obvious protrusions,and the safranine staining was completely stained;compared with sham operation group,cartilage of arthritis group showed protrusions,and the staining was completely lost,the arthritis index,serum and cartilage tissue TNF-α,IL-6,IL-1β contents,cartilage tissue NF-κB p65,ERK protein phosphoryla-tion degrees were increased significantly(P<0.05);compared with arthritis group,cartilage tissue of nimesulide group and shikonin group gradually recovered,the safranine staining was increased,the arthritis index,serum and cartilage tissue TNF-α,IL-6,IL-1β contents,cartilage tissue NF-κB p65,ERK protein phosphorylation degrees were reduced significantly(P<0.05);compared with shi-konin group,shikonin+ERK activation group and shikonin+NF-κB activation group showed a slower recovery of cartilage tissue and se-rious loss of safranine staining,the arthritis index,serum and cartilage tissue TNF-α,IL-6,IL-1β contents,cartilage tissue NF-κB p65,ERK protein phosphorylation degrees were increased significantly(P<0.05);there was no significant difference of each index be-tween shikonin group and nimesulide group(P>0.05).Conclusion:Shikonin can relieve knee osteoarthritis by regulating the NF-κB/ERK pathway and inhibiting the activation of related proteins.