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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
Δ
肖博文 ,彭 聪,张森伟(荆州市中心医院疼痛科,湖北 荆州 434000)
*
中图分类号 R285;R965 文献标志码 A 文章编号 1001-0408(2026)01-0049-06
DOI 10.6039/j.issn.1001-0408.2026.01.09
摘 要 目的 研究槲皮素(QUE)对腰椎间盘突出症(LDH)大鼠椎间盘退变的影响,并基于叉头框蛋白O3/沉默信息调节因子1
(FOXO3/Sirt1)通路探讨其作用机制。方法 构建LDH大鼠模型,将造模成功的大鼠随机分为LDH组(灌胃+腹腔注射等体积生
理盐水)、QUE-L组(灌胃50 mg/kg的QUE+腹腔注射等体积生理盐水)、QUE-H组(灌胃100 mg/kg的QUE+腹腔注射等体积生理
盐水)、QUE-H+EX-527(Sirt1抑制剂)组(灌胃100 mg/kg的QUE+腹腔注射1 mg/kg的EX-527溶液),每组12只;另取12只正常健
康大鼠作为Control组(灌胃+腹腔注射等体积生理盐水)。每天给药1次,连续8周。末次给药后,检测大鼠疼痛阈值、血清中炎症
因子水平,观察大鼠椎间盘组织病理损伤,检测大鼠椎间盘组织髓核细胞凋亡情况,检测大鼠椎间盘组织中基质金属蛋白酶 3
(MMP-3)、磷脂酶A2(PLA2)以及凋亡、FOXO3/Sirt1通路相关蛋白表达。结果 与LDH组比较,QUE-L组、QUE-H组大鼠椎间盘
组织病理损伤显著改善;机械缩足反射阈值、热刺激缩足反射潜伏期,血清中转化生长因子β1、白细胞介素10(IL-10)水平,椎间盘
组织中B细胞淋巴瘤2(Bcl-2)、FOXO3、Sirt1蛋白的相对表达量均显著升高/延长(P<0.05);血清中肿瘤坏死因子α、IL-1β水平,
椎间盘组织病理评分,髓核细胞凋亡率,椎间盘组织中MMP-3、PLA2的阳性表达率和Bcl-2相关X蛋白的相对表达量均显著降低
(P<0.05);与 QUE-H 组比较,QUE-H+EX-527 组大鼠椎间盘组织病理损伤加重,以上指标的变化趋势均发生了显著逆转(P<
0.05)。结论 QUE可改善LDH大鼠椎间盘退变,其机制可能与激活FOXO3/Sirt1通路有关。
关键词 槲皮素;腰椎间盘突出症;叉头框蛋白O3;沉默信息调节因子1;凋亡
Exploration of the effects of quercetin on intervertebral disc degeneration in lumbar intervertebral disc
herniation rats based on the FOXO3/Sirt1 pathway
XIAO Bowen,PENG Cong,ZHANG Senwei(Dept. of Pain Medicine, Jingzhou Central Hospital, Hubei
Jingzhou 434000, China)
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
Δ 基金项目 2024年度荆州市科技计划项目(No.2024HD08)
*第一作者 主治医师,硕士。研究方向:脊柱退变。E-mail: trends of all the above indicators were significantly reversed
zvrpnd@163.com (P<0.05). CONCLUSIONS QUE can ameliorate intervertebral
中国药房 2026年第37卷第1期 China Pharmacy 2026 Vol. 37 No. 1 · 49 ·

