探讨芪麝丸及其有效成分延缓髓核细胞衰老的机制研究OA

[Objective]To investigate the mechanism by which Qishe Pills(QSP)and its effective components delay intervertebral disc degeneration(IVDD)and nucleus pulposus(NP)cell senescence,utilizing network pharmacology and experimental validation.[Methods]Active components of QSP and their potential targets were screened based on network pharmacology,and a"Component-Target-Pathway"network was constructed.The binding affinity between active components of QSP and key targets of relevant signaling pathways was validated by molecular docking.Combined with in vitro experiments,an NP cell senescence model was established.Effective monomers were identified,and the upstream-downstream relationships of their action pathways were explored using Western blot and immunofluorescence assays.[Results]Network pharmacology revealed that the intersection targets were significantly enriched in the p53 signaling pathway and were associated with the PI3K/AKT,AMPK/SIRT1,ERK,and TGF-β/Smad pathways.Molecular docking and experimental validation identified tetrandrine as the effective component of QSP regulating IVDD.In vitro experiments confirmed that tetrandrine inhibits p53 pathway activity via the upstream PI3K/AKT/MDM2 pathway,thereby reducing NP cell apoptosis and promoting the synthesis of type II collagen(COL2A1).[Conclusion]NP cell senescence is a key pathological factor in IVDD.This study elucidates the mechanism by which QSP delay IVDD,identifies tetrandrine as its effective component,and demonstrates that tetrandrine mitigates IVDD and NP cell senescence by regulating the PI3K/AKT signaling pathway.