补肾痹通方调控Hippo/YAP通路治疗膝骨关节炎大鼠的作用机制OA

Objective:To investigate the effects of Bushen Bitong formula(BSBTF)on chondrocyte apoptosis in knee oste-oarthritis(KOA)rats by modulating the Hippo/YAP signaling pathway.Methods:Sixty SD rats weighing approximately 200 g were randomly assigned using a random number table to the following groups:low-dose BSBTF group(BSBTF-L,21.25 g/kg),high-dose BSBTF group(BSBTF-H,42.50 g/kg),high-dose BSBTF(42.50 g/kg)+VTPF(YAP inhibitor 10 mg/kg)group,sham-operated group,and model group,with 12 rats per group.The Huhth method was used to induce a rat knee osteoarthritis model.After 4 weeks of modeling,oral administration began for 4 weeks.General daily activities and radiographic examinations were observed.Hematoxylin-eosin(HE)staining and Alcian blue staining were performed to examine knee cartilage tissue lesions.Serum levels of in-terleukin-6(IL-6),interleukin-1β(IL-1β),and tumor necro-sis factor-α(TNF-α)were detected using ELISA;Immuno-histochemistry assessed p-YAP and YAP protein expres-sion;qPCR measured mRNA expression levels of YAP,ADAMTS-5,and MMP-13 in knee cartilage tissue;Western Blot analysis was used to detect p-YAP,YAP,and CTGF protein expression.Results:Compared with the sham-operated group,rats in the model group exhibited lethargy,reduced activity,and poor appetite.Radiographic examination revealed marked narrowing or even disappearance of the joint space,roughening of the tibial plateau surface,sclerosis of the distal femur,and osteophyte formation,with severe cartilage tissue destruction.p-YAP protein expression decreased,while IL-1β,IL-6,TNF-α levels,and YAP/CTGF protein expression in-creased(P<0.05).Compared to the model group,the BSBTF-L and BSBTF-H groups exhibited opposite trends in these indicators(P<0.05),with higher doses yielding more pronounced effects.Compared to the high-dose BSBTF group,the high-dose BSBTF+VTPF group showed minimal changes in YAP and p-YAP expression.However,IL-1β,IL-6,TNF-α levels,mRNA expression levels related to ADAMTS-5 and MMP-13,and CTGF protein expression were significantly re-duced(P<0.05).Conclusion:BSBTF may delay cartilage degeneration in KOA rats by activating the Hippo/YAP signa-ling pathway.