中国中医骨伤科杂志2026,Vol.34Issue(3):7-15,9.DOI:10.20085/j.cnki.issn1005-0205.260302
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
Study on the Mechanism of Bushen Bitong Formula in Regulating the Hippo/YAP Pathway to Treat Knee Osteoarthritis in Rats
摘要
Abstract
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.关键词
膝骨关节炎/补肾痹通方/河马信号通路/关节软骨/软骨基质Key words
knee osteoarthritis/Bushen Bitong formula/Hippo signaling pathway/articular cartilage/cartilage matrix分类
医药卫生引用本文复制引用
王鹏光,李逸统,热米拉·艾买提,牟利民,方锐..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[J].中国中医骨伤科杂志,2026,34(3):7-15,9.基金项目
国家自然科学基金地区科学基金项目(82360934)新疆维吾尔自治区科学技术厅科技创新领军人才项目—高层次领军人才项目(2022TSYCLJ0007) (82360934)