杨梅素调节Wnt/β-catenin信号通路对腰椎间盘突出症大鼠椎间盘退变的影响

doi:10.3969/j.issn.1006-6233.2024.10.09

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摘要 目的:探究杨梅素(MYR)调节Wnt/β-连环蛋白(β-catenin)信号通路对腰椎间盘突出症(LDH)大鼠椎间盘退变的影响。方法:将大鼠随机分为Sham组、LDH组、MYR组、MYR+LiCl组(Wnt/β-catenin信号通路激活剂),每组12只,除Sham组外采用自体髓核移植法复制LDH大鼠模型,造模成功后进行药物干预,每天1次,持续28d。von Frey Hair纤维丝、辐射热痛觉测分析大鼠疼痛敏化行为;ELISA法检测血清肿瘤坏死因子(TNF-α)、白细胞介素1β(IL-1β)水平;HE染色法观察椎间盘组织病理变化;TUNEL染色法测定髓核细胞凋亡;免疫组化检测大鼠椎间盘组织中基质金属蛋白酶(MMP)13表达;Western blot分别检测Wnt/β-catenin信号通路蛋白表达。结果:与Sham组比较,LDH组大鼠髓核细胞皱缩、排列不规则,数量减少,纤维环破裂,MWT与TWL降低,TNF-α、IL-1β含量、椎间盘组织病理评分、髓核细胞凋亡率、MMP13、Wnt3a、β-catenin表达升高(P<0.05);与LDH组比较,MYR组髓核细胞形态、纤维环结构显著改善,大鼠MWT与TWL升高,TNF-α、IL-1β含量、椎间盘组织病理评分、髓核细胞凋亡率、MMP13、Wnt3a、β-catenin表达降低(P<0.05);Wnt/β-catenin信号通路激活剂LiCl可升高血清炎症因子水平,促进髓核细胞凋亡,加重椎间盘组织病理损伤,减弱了MYR对LDH大鼠椎间盘退变的延缓作用(P<0.05)。结论:MYR可能通过抑制Wnt/β-catenin信号通路的激活,降低炎症反应,减少髓核细胞凋亡,从而改善LDH大鼠的椎间盘退变。

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关键词 ：杨梅素, Wnt/β-catenin信号通路, 腰椎间盘突出症, 椎间盘退变

Abstract：Objective: To investigate the effect of myricetin (MYR) on intervertebral disc degeneration (IVDD) in rats with lumbar disc herniation (LDH) by regulating the Wnt/β-catenin signaling pathway. Methods: Rats were randomly divided into four groups: Sham group, LDH group, MYR group, and MYR+LiCl group (Wnt/β-catenin signaling pathway activator), with 12 rats in each group. Except for the Sham group, an LDH rat model was replicated using autologous nucleus pulposus transplantation. After successful model establishment, drug intervention was performed once daily for 28 days. Von Frey hair filaments and radiant heat pain tests were used to analyze the pain sensitization behavior of rats. ELISA was used to detect the levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in serum. HE staining was used to observe the pathological changes of intervertebral disc tissue. TUNEL staining was used to determine the apoptosis of nucleus pulposus cells. Immunohistochemistry was used to detect the expression of matrix metalloproteinase 13 (MMP13) in rat intervertebral disc tissue. Western blot was used to detect the protein expression of the Wnt/β-catenin signaling pathway. Results: Compared with the Sham group, rats in the LDH group showed shrinkage and irregular arrangement of nucleus pulposus cells, reduced cell number, and annulus fibrosus rupture. MWT and TWL were decreased, while TNF-α, IL-1β levels, disc tissue pathological score, nucleus pulposus cell apoptosis rate, MMP13, Wnt3a and β-catenin expression were increased (P<0.05). Compared with the LDH group, MYR group showed significant improvement in nucleus pulposus cell morphology and annulus fibrosus structure, increased MWT and TWL, and decreased TNF-α, IL-1β levels, disc tissue pathological score, nucleus pulposus cell apoptosis rate, MMP13, Wnt3a, and β-catenin expression (P<0.05). Wnt/β-catenin signaling pathway activator LiCl increased serum levels of inflammatory factors, promoted nucleus pulposus cell apoptosis, aggravated disc tissue pathological damage, and weakened the delaying effect of MYR on IVDD in LDH rats (P<0.05). Conclusion: Myricetin may improve intervertebral disc degeneration in LDH rats by inhibiting the activation of the Wnt/β-catenin signaling pathway, reducing inflammation, and decreasing nucleus pulposus cell apoptosis.

Key words： Myricetin Wnt/β-catenin signaling pathway Lumbar disc herniation Intervertebral disc degeneration

基金资助:2023年度河北医学科学研究课题计划,(编号:20232139)

引用本文:

李娜, 张鹏, 张楠, 林伟, 刘德峰, 郑继会. 杨梅素调节Wnt/β-catenin信号通路对腰椎间盘突出症大鼠椎间盘退变的影响[J]. 河北医学, 2024, 30(10): 1634-1638.
LI Na, ZHANG Peng, ZHANG Nan, et al. Effect of Myricetin on Intervertebral Disc Degeneration in Rats with Lumbar Disc Herniation by Regulating Wnt/β-catenin Signaling Pathway. HeBei Med, 2024, 30(10): 1634-1638.

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http://www.hbyxzzs.cn/CN/10.3969/j.issn.1006-6233.2024.10.09 或 http://www.hbyxzzs.cn/CN/Y2024/V30/I10/1634

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