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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
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| 篇名： | 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 |
| TITLE： | Exploration of the effects of quercetin on intervertebral disc degeneration in lumbar intervertebral disc herniation rats based on the FOXO3/Sirt1 pathway |
| 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50mg/kg的QUE+腹腔注射等体积生理盐水）、QUE-H组（灌胃100mg/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100mg/kg的QUE+腹腔注射1mg/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。 |
| 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. |
| 期刊： | 2026年第37卷第01期 |
| 作者： | 肖博文；彭聪；张森伟 |
| AUTHORS： | XIAO Bowen，PENG Cong，ZHANG Senwei |
| 关键字： | 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 |
| KEYWORDS： | quercetin； lumbar intervertebral disc herniation； FOXO3； Sirt1； apoptosis |
| 阅读数： | 41 次 |
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