右归丸经p38 MAPK/NF-κB通路抑制膝骨性关节炎软骨细胞凋亡OA

Objective To investigate the mechanism by which Yougui Pill(右归丸,YGP)inhibits chondrocyte apoptosis in rats with knee osteoarthritis(KOA)based on the p38 mitogen-activated protein kinase(p38 MAPK)/nuclear factor kappa-B(NF-κB)signaling pathway.Methods Forty specific pathogen-free(SPF)-grade Wistar rats were randomly divided into 4 groups.After successful model establishment,the control and model groups were given equal volumes of normal saline via gavage,while celecoxib group received cele-coxib solution and YGP group received YGP solution via gavage,once daily for 28 consecutive days.Knee joint specimens were sub-jected to HE staining and TUNEL staining.Serum levels of interleukin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)were measured by enzyme-linked immunosorbent assay(ELISA).Immunofluorescence assay was employed to detect the pro-tein expressions of Bcl-2,Bcl-xl,Bax,and Caspase-3 in articular cartilage.Western blot(WB)was used to determine the protein expressions of P38 MAPK,phosphorylated(p)-P38 MAPK,NF-κB p65,p-NF-κB p65,Bcl-2,Bax,and Caspase-3 in articular carti-lage.Reverse transcription-polymerase chain reaction(RT-PCR)was applied to detect the P38 MAPK mRNA and NF-κB p65 mRNA expression levels.Results Compared with the celecoxib group,the YGP group showed a lower degree of joint swelling,smaller knee joint circumference and toe volume,a lower chondrocyte apoptosis rate,and decreased serum levels of IL-1β,IL-6,and TNF-α(P<0.05).Additionally,the YGP group exhibited lower protein expressions of p-P38 MAPK,p-NF-κB p65,Bax,and Caspase-3,but higher expressions of Bcl-2 and Bcl-xl in cartilage compared with the celecoxib group(P<0.05).Furthermore,compared with the cele-coxib group,the mRNA expressions of P38 MAPK and NF-κB p65 in cartilage were significantly lower in the YGP group(P<0.05).Conclusion YGP can regulate chondrocyte apoptosis and improve osteoarthritis symptoms in KOA rats by modulating the p38 MAPK/NF-κB signaling pathway.