Exploration of the effects of quercetin on intervertebral disc degeneration in lumbar intervertebral disc herniation rats based on the FOXO3/Sirt1 pathway
- VernacularTitle:基于FOXO3/Sirt1通路探讨槲皮素对腰椎间盘突出症大鼠椎间盘退变的影响
- Author:
Bowen XIAO
1
;
Cong PENG
1
;
Senwei ZHANG
1
Author Information
1. Dept. of Pain Medicine,Jingzhou Central Hospital,Hubei Jingzhou 434000,China
- Publication Type:Journal Article
- Keywords:
quercetin;
lumbar intervertebral disc herniation;
FOXO3;
Sirt1;
apoptosis
- From:
China Pharmacy
2026;37(1):49-54
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To investigate the effects of quercetin (QUE) on intervertebral disc degeneration in rats with lumbar intervertebral disc herniation (LDH) and explore its mechanism based on the forkhead box protein O3/silent information regulator 1 (FOXO3/Sirt1) pathway. METHODS A rat model of LDH was established. The successfully modeled rats were randomly divided into LDH group (gavaged with and intraperitoneally injected with an equal volume of normal saline), QUE-L group (gavaged with 50 mg/kg QUE+intraperitoneally injected with an equal volume of normal saline), QUE-H group (gavaged with 100 mg/kg QUE+ intraperitoneally injected with an equal volume of normal saline), and QUE-H+EX-527 (a Sirt1 inhibitor) group (gavaged with 100 mg/kg QUE+intraperitoneally injected with 1 mg/kg EX-527), with 12 rats in each group. Additionally, 12 healthy normal rats were selected as the control group (gavaged with and intraperitoneally injected with an equal volume of normal saline). All rats were administered the corresponding agents once daily for consecutive 8 weeks. After the final administration, the pain threshold and serum levels of inflammatory factors in rats were measured; pathological damage of lumbar intervertebral disc tissue was observed, the apoptosis of nucleus pulposus cells in lumbar intervertebral disc tissue was assessed, and the expression levels of matrix metalloproteinase-3 (MMP-3), phospholipase A2 (PLA2), as well as apoptosis-related proteins and FOXO3/Sirt1 pathway- related proteins in intervertebral disc tissue were determined. RESULTS Compared with LDH group, pathological damage of intervertebral disc tissue were improved significantly in QUE-L group and QUE-H group; paw withdrawal mechanical threshold, paw withdrawal thermal latency, the serum levels of transforming growth factor-β1 and interleukin-10 (IL-10) as well as the expression levels of B-cell lymphoma-2 (Bcl-2), FOXO3 and Sirt1 were significantly increased or prolonged (P<0.05). Serum levels of tumor necrosis factor-α and IL-1β, histopathological score of intervertebral disc tissue, apoptotic rate of nucleus pulposus cells, positive expressions of MMP-3 and PLA2 in intervertebral disc tissue and expression levels of Bcl-2 associated X protein were significantly decreased (P<0.05). Compared with the QUE-H group, the QUE-H+EX-527 group presented aggravated pathological damage of intervertebral disc tissue, and the trends of all the above indicators were significantly reversed(P<0.05). CONCLUSIONS QUE can ameliorate intervertebral disc degeneration in LDH rats, and its mechanism may be related to the activation of the FOXO3/Sirt1 pathway.