Molecular insights into Atorvastatin's role in delaying intervertebral disc degeneration

This study aimed to investigate the molecular mechanisms and effects of atorvastatin (Ator) in delaying intervertebral disc degeneration (IDD), with a particular focus on its role in modulating oxidative stress and apoptosis in nucleus pulposus cells (NPCs) via the Nrf2 signaling pathway.

In vitro, rat NPCs were treated with different concentrations of atorvastatin, and the optimal concentration was determined using the Cell Counting Kit-8 (CCK-8) assay. Reactive oxygen species (ROS) levels were measured using a ROS detection kit, while apoptosis was evaluated by flow cytometry and TUNEL assays. Western blotting was performed to assess the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), its downstream antioxidant proteins, and apoptosis-related proteins. In vivo, fifteen rats were randomly assigned to control, acupuncture, and atorvastatin injection groups. After four weeks of treatment, intervertebral discs were collected for histological evaluation using hematoxylin-eosin (HE) and Flip-Red O staining. Apoptosis within the discs was further examined by electron microscopy.

Pretreatment with 10 μM atorvastatin significantly improved the survival rate of NPCs exposed to hydrogen peroxide (H₂O₂) and reduced apoptosis. Atorvastatin enhanced the antioxidant capacity of NPCs and decreased intracellular ROS accumulation. It promoted Nrf2 activation and upregulated the expression of downstream antioxidant factors, thereby exerting a protective effect against oxidative stress-induced injury. Inhibition of Nrf2 attenuated these protective effects of atorvastatin. Moreover, atorvastatin reduced the expression of apoptosis-related proteins and inhibited H₂O₂-induced extracellular matrix degradation in chondrocytes. In the in vivo rat model, atorvastatin treatment ameliorated histological signs of intervertebral disc degeneration and reduced apoptosis in disc tissues.

These findings indicate that atorvastatin alleviates H₂O₂-induced oxidative stress and apoptosis in NPCs predominantly through activation of the Nrf2 signaling pathway, leading to preservation of extracellular matrix integrity and attenuation of disc degeneration. Collectively, the data support the potential of atorvastatin as a therapeutic agent for the prevention or treatment of lumbar intervertebral disc degeneration.