Acupuncture alleviates the progression of lumbar disc herniation by regulating the autophagy level of nucleus pulposus cells through the SIRT1/Sestrin2 pathway

Background and purpose: Lumbar disc herniation (LDH) is a degenerative spine disease and the most common cause of lower back pain, with a high prevalence in younger patients. The use of acupuncture (AC) as a conservative treatment for LDH has received widespread attention at home and abroad. Therefore, the present study aimed to investigate the specific mechanism of AC in the treatment of LDH.

Methods: In this study, we established an LDH rat model via autologous nucleus pulposus (NP) transplantation and treated human NP cells with 50 μM tert-butyl hydroperoxide (TBHP) for 24h to establish an LDH cell model for experimental investigation. The damage to human NP cells and the development of LDH in rats were evaluated via CCK-8, flow cytometry, H&E staining, and Safranin O-Fast Green staining, and the expression of related proteins was detected via western blotting.

Results: This study revealed that AC promoted the protein expression of Collagen II, Bcl-2, LC3II/I, and Beclin1, and inhibited the protein expression of Bax, Cleaved Caspase-3, and p62, thereby improving the pathological condition of lumbar NP tissue in rats and alleviating LDH progression. In addition, SIRT1 and Sestrin2 are expressed at low levels in LDH, and the overexpression of SIRT1 or Sestrin2 can improve NP cell viability and inhibit cell Apoptosis by activating Autophagy. Mechanistically, AC inhibits the MDM2-mediated ubiquitination of Sestrin2 by upregulating SIRT1 expression, thereby promoting Sestrin2 expression, activating Autophagy, and ultimately alleviating the development of LDH.

Conclusion: AC relieves the development of LDH by activating the SIRT1/Sestrin2 Autophagy pathway. Our study provides a new molecular mechanism for the AC treatment of LDH.