河北中医药学报2025，Vol.40Issue(6)：14-21,8.
独活寄生汤调节Hippo-YAP信号通路抑制膝骨关节炎大鼠滑膜细胞凋亡的机制研究
Mechanism of Duhuo Jisheng Decoction Regulating Hippo-YAP Pathway to Inhibit Synoviocyte Apoptosis in KOA Rats
摘要
Abstract
Objective:To observe the therapeutic effect of Duhuo Jisheng Decoction on knee osteoarthritis(KOA)rats induced by type Ⅱ collagenase,and to preliminarily explore its mechanism of action based on the Hippo-Yes-associated protein(YAP)signaling pathway.Methods:SD rats were randomly divided into the normal group,model group,and high-and low-dose Duhuo Jisheng Decoc-tion groups.The KOA model was established by intra-articular injection of type Ⅱ collagenase.The high-and low-dose Duhuo Jisheng Decoction groups were given corresponding doses of Duhuo Jisheng Decoction by gavage for 14 days.During the experiment,the general condition and knee joint swelling degree were recorded,and MicroCT was used to observe the changes in cartilage tissue structure.After the experiment,HE staining was used to observe the pathological morphological changes of knee joint synovial tissue.Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL)staining was used to detect the apoptosis of knee joint synovi-al cells.Quantitative real-time polymerase chain reaction(qRT-PCR)was used to detect the mRNA expression levels of Yes-associated protein 1(YAP1),transcriptional co-activator with PDZ-binding motif(TAZ),matrix metalloproteinase-3(MMP3),interleukin-6(IL-6),interleukin-1β(IL-1β),and tumor necrosis factor-α(TNF-α)in synovial tissue.Western blot was used to detect the protein expression levels of YAP1,TAZ,Bcl-2-associated X protein(Bax),B-cell lymphoma-2(Bcl-2),and Caspase3 in synovial tissue.Results:Compared with the normal group,the model group showed significant knee joint swelling,increased fibroblasts with uneven cell morphology,enhanced cell apoptosis,sparse trabecular bone arrangement,reduced trabecular bone number,and increased trabec-ular bone volume and separation.In the synovial tissue of the model group,the mRNA expression levels of YAP1 and TAZ were de-creased,while those of MMP3,IL-6,IL-1β,and TNF-α were increased(P<0.05);the protein expressions of YAP1,TAZ,and Bcl-2 were decreased(P<0.05),while those of Bax and Caspase3 were increased(P<0.05).Compared with the model group,both high-and low-dose groups exhibited reduced knee joint swelling,decreased fibroblasts with improved cell morphology,reduced cell apoptosis,and subchondral trabecular bone with denser arrangement,increased number,and decreased separation and volume.Additionally,in the synovial tissue of the treatment groups,the mRNA expressions of YAP1 and TAZ were increased(P<0.05),while those of MMP3,IL-6,IL-1β,and TNF-α were decreased(P<0.05);YAP1,TAZ,and Bcl-2 were increased(P<0.05),while those of Bax and Caspase3 were decreased(P<0.05).Conclusion:Duhuo Jisheng Decoction can alleviate the inflammatory re-sponse in type Ⅱ collagenase-induced KOA rats,and its therapeutic effect may be exerted by activating the Hippo-YAP signaling path-way and reducing the levels of inflammatory factors.关键词
膝骨关节炎/独活寄生汤/滑膜/Hippo-YAP信号通路/细胞凋亡Key words
KOA/Duhuo Jisheng Decoction/synovium/Hippo-YAP signaling pathway/apoptosis分类
医药卫生引用本文复制引用
PANG Zixuan,LIU Wei,WEI Danyang,ZHANG Ruixiao,MA Zhoupei,ZHANG Zhenqun,WANG Xi..独活寄生汤调节Hippo-YAP信号通路抑制膝骨关节炎大鼠滑膜细胞凋亡的机制研究[J].河北中医药学报,2025,40(6):14-21,8.基金项目
国家自然科学基金青年项目(81503268) （81503268）
河北省自然科学基金中医药联合基金项目(H2022423305) （H2022423305）
河北省中医药管理局科研计划项目(2023014) （2023014）
