Molecular Insights into Atorvastatin's Role in Delaying Intervertebral Disc Degeneration

Yupeng Li^1,2Linghao Wang^1,2Xingjie Wang^1,3Kang Li^1,4Qian Wang^1,4Kai Gao^1,5Cunxin Zhang^1,4,5*Chaoliang Lv^1,4*

• ¹Jining NO.1 People's Hospital Affiliated to Shandong First Medical University & Shandong Academy of Medical Sciences, Jining, China
• ²Jining Medical University, Jining, China
• ³Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China
• ⁴Shandong Provincial Key Medical and Health Laboratory of Neuroinjury and Repair, Jining, China
• ⁵Medical Integration and Practice Center, Shandong University, Jinan, China

This study aims to investigate the molecular mechanisms and effects of atorvastatin (Ator) in delaying intervertebral disc degeneration (IDD). Initially, we determined the optimal concentration of atorvastatin in rat nucleus pulposus cells (NPCs) in vitro using the Cell Counting Kit-8 (CCK-8) assay. Reactive oxygen species (ROS) levels in NPCs were measured using a detection kit, and apoptosis was assessed via flow cytometry and TUNEL assays. Additionally, western blotting was performed to analyze the levels of nuclear factor erythroid 2–related factor 2 (Nrf2), its downstream proteins, and apoptosis-related proteins. Concurrently, an in vivo study was conducted in which fifteen rats were divided into control, acupuncture, and atorvastatin injection groups. After four weeks, intervertebral discs were harvested for histological evaluation using hematoxylin-eosin (HE) staining and Flip-Red O staining. Apoptosis levels in the discs were also analyzed using electron microscopy. The results demonstrated that pretreatment with 10 μM atorvastatin improved the survival rate of nucleus pulposus cells induced by hydrogen peroxide (H2O2) and reduced apoptosis. Moreover, atorvastatin enhanced the antioxidant capacity of NPCs and decreased ROS accumulation. Our findings further revealed that atorvastatin exerted a protective effect on oxidative stress-induced phagocytes by promoting Nrf2 activation and the expression of its downstream antioxidant factors. Conversely, inhibition of Nrf2 attenuated the protective effects of atorvastatin. Importantly, atorvastatin reduced the expression of apoptosis-related proteins and inhibited H2O2-induced extracellular matrix degradation in chondrocytes. In conclusion, atorvastatin alleviates H2O2-induced This is a provisional file, not the final typeset article oxidative stress in nucleus pulposus cells via the Nrf2 signaling pathway, supporting its potential as a therapeutic agent for lumbar intervertebral disc degeneration.