Investigating Effect of Yougui Pill(右归丸)on Chondrocyte Apoptosis in Knee Osteoarthritis Model Rats Based on RAP1 Signaling
Objective To explore the treatment of knee osteoarthritis(KOA)model rats with Yougui Pill(右归丸),observe the morphology of rat articular cartilage,detect the effect of Yougui Pill on the expression of RAP1 signaling pathway and the expres-sions of inflammatory factors in the serum and explore the mechanism of Yougui Pill on the expression of RAP1 signaling pathway and the prevention and treatment of KOA so as to provide a theoretical basis for treatment.Methods Seventy-two SPF SD rats(half male and half female)were randomly divided into sham operation group(n=12)and modeling group(n=60).The KOA model was established by modified Hulth method in the model group,and sham operation group received sham operation.The rats were divided into model group(n=11),Yougui Pill low-dose group(n=12),Yougui Pill medium-dose group(n=12),You-gui Pill high-dose group(n=12)and celecoxib group(n=12).The model group and sham operation group were given 0.9％sodium chloride solution at the administration stage.The low-dose group of Yougui Pill was 1/2 of the equivalent concentration(0.5 g/d).The equivalent concentration of the medium-dose group of Yougui Pill was 1 g/d and the high-dose group of You-gui Pill was twice the equivalent concentration(2 g/d).Celecoxib group was configured as suspension(the equivalent concentra-tion was 0.007 2 g/d).After 7 weeks of driving,cartilage pathology,serum contents of tumor necrosis factor-α(TNF-α),in-terleukin-1β(IL-1β)and interleukin-18(IL-18),and the expression levels of RAP1,RAF,MEK1/2,ERK1/2,CREB,MMP3,MMP13,ADAMTS,C-fos,C-myc and C-Jun in cartilage tissue were detected and compared in each group.Results Pathological examination results of cartilage in each group of rats showed that abnormalities were found in the cartilage tissue of rats in the sham operation group.There were significant defects in some areas of the joint cartilage of the model group rats.The surface wear in the Yougui Pill low-dose group was reduced compared to that of the model group.However,the ero-sion phenomenon on the cartilage surface of rats in the Yougui Pill medium-dose group,Yougui Pill high-dose group and the Western medicine group was significantly improved.Compared with those of the model group,the contents of IL-1β,TNF-αand IL-18 in Yougui Pill low-dose group,Yougui Pill medium-dose group and Yougui Pill high-dose group were obviously decreased with statistical significance.The detection results of RAP1 RAF MEKL/2-ERKL/2-CREB signaling pathway activa-tion level showed that compared with those of the sham operation group,the expressions of RAP1,RAF,MEK1/2,ERK1/2,CREB,MMP3,MMP13,ADAMTS,C-fos,C-myc and C-Jun were significantly increased(P＜0.01)with statistical signifi-cance.The results indicated that during the occurrence of KOA,the RAP1-RAF-MEKl/2-ERKL/2-CREB signaling path-way was activated,inflammation and cell apoptosis in cartilage tissue were mediated,which was consistent with the previous re-search results.After intervention with Yougui Pill,the expression levels of RAP1,RAF,MEK1/2,ERK1/2,CREB,MMP3,MMP13,ADAMTS,C-fos,C-myc and C-Jun proteins in cartilage tissue were significantly reduced(P＜0.01)with statistical significance.Conclusions Yougui Pill can inhibit the activation of RAP1-RAF-MEK1/2-ERK1/2-CREB signaling Pathway in cartilage tissue of KOA rats,reduce the expression of inflammatory factors,and thus reduce chondrocyte apoptosis.
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