This study aims to investigate the mechanism of Huangqin Qingre Chubi Capsules(HQC)in delaying chondrocyte senescence of osteoarthritic(OA)rats by regulating the p53/p21 signaling pathway.Rheumatic fever paralysis models of OA rats were induced based on monosodiun iodoacetate(MIA)combined with external rheumatic fever environmental stimuli and divided into normal(Con)group,OA model(MIA)group,OA model+rheumatic fever stimulation model(MIA-M)group,MIA-M+HQC low-dose(MIA-M+HQC-L)group,medium-dose(MIA-M+HQC-M)group,and high-dose(MIA-M+HQC-H)group,and MIA-M+glucosamine(MIA-M+GS)group.The models were successfully prepared and administered by gavage for 30 d.The pathological changes of cartilage were observed by hematoxylin-eosin(HE)and Senna O solid green(SO)staining.The expression of interleukin(IL)-1β and IL-6 was detected by enzyme-linked immunosorbent assay(ELISA).Flow cytometry(FCM)was used to detect apoptosis and cell cycle.The mRNA expression of MMP13,ADAMTS-5,COLⅡ,and TGF-β was detected by RT-qPCR.The protein expression of p53/p21,p16,Bax,and Bcl-2 was detected by Western blot.The articular cartilage surface of rats in the Con group was smooth,and the tide line was smooth.The cartilage layer of MIA and MIA-M groups was obviously damaged,and the cartilage matrix was reduced.The above conditions were more severe in the MIA-M group.The cartilage surface of the HQC high-dose group and MIA-M+GS group was basically intact with clear delamination.Compared with the MIA-M+HQC-H group,Mankin's score was higher in the HQC low-dose and medium-dose groups,and the change was not obvious in the MIA-M+GS group.Compared with the Con group,the proportion of chondrocytes G1 was elevated in the MIA and MIA-M groups,and the proportion of the S phase and G2 phase was significantly decreased.In addition,the apoptosis rate was increased.Compared with MIA-M,HQC groups inhibited apoptosis and promoted cell proliferation in a concentration-dependent manner.Compared with the MIA-M+HQC-H group,the effect was more significant in the HQC high-dose group than in the HQC medium-low dose,while it was not significant in the MIA-M+GS group.Compared with the Con group,IL-1β and IL-6 were elevated in the MIA and MIA-M groups,and mRNA levels of MMP13 and ADAMTS-5 were elevated.p53,p21,p16,and Bax protein were elevated,and mRNA levels of COLⅡ and TGF-β were decreased.Compared with the MIA-M group,IL-1β and IL-6 decreased after drug interventions of HQC and GS,and mRNA levels of MMP13 and ADAMTS-5,as well as protein levels of p53,p21,Bax,and p16 decreased.In addition,Bcl-2 increased.The improvement of these indexes was significantly better in the MIA-M+HQC-H group than in the HQC low-dose and medium-dose groups,and the difference with the MIA-M+GS group was not significant.HQC delayed MIA-induced chondrocyte senescence in OA rats,inhibited inflammatory response and extracellular matrix(ECM)degradation,and its mechanism may be related to the inhibition of the p53/p21 pathway.
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