基础医学与临床 ›› 2023, Vol. 43 ›› Issue (1): 116-122.doi: 10.16352/j.issn.1001-6325.2023.01.0116

• 研究论文 • 上一篇    下一篇

二甲双胍抑制腰椎间盘退变模型兔椎间盘组织的细胞凋亡

董军立, 蔡少康, 严蕾, 蔡毅*   

  1. 华中科技大学同济医学院附属武汉中心医院 疼痛科, 湖北 武汉 430014
  • 收稿日期:2022-03-28 修回日期:2022-06-28 发布日期:2022-12-27
  • 通讯作者: *iu4ztm@163.com
  • 基金资助:
    武汉市卫生和计划生育委员会资助项目(WX18Q23)

Metformin inhibits the apoptosis of intervertebral disc tissue cells in rabbit model with lumbar intervertebral disc degeneration

DONG Junli, CAI Shaokang, YAN Lei, CAI Yi*   

  1. Department of Pain Management, the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, China
  • Received:2022-03-28 Revised:2022-06-28 Published:2022-12-27
  • Contact: *iu4ztm@163.com

摘要: 目的 探究二甲双胍对兔椎间盘组织自噬及炎性反应的影响,以初步探究其抗椎间盘退变的分子机制。方法 将兔分为:假手术组、模型组、二甲双胍组、自噬抑制剂组、二甲双胍+自噬抑制剂组,每组10只。免疫组化染色法检测自噬相关蛋白7(Atg7)阳性表达;Western blot检测自噬相关蛋白LC3Ⅱ、Beclin1、溶酶体相关膜蛋白2(LAMP2)、肿瘤坏死因子-α(TNF-α)、IL-1β、凋亡相关蛋白caspase-8表达。结果 与模型组相比,二甲双胍组兔椎间盘退变减轻,自噬小体及自噬溶酶体形成增多,自噬蛋白质表达增多,炎性因子及凋亡蛋白质表达降低(P<0.05)。自噬抑制剂可抑制自噬,加重椎间盘退变,增强炎性因子及凋亡蛋白质表达,并减弱二甲双胍发挥的增强自噬、减弱炎性反应及凋亡作用(P<0.05)。结论 二甲双胍可能通过促进自噬激活,减弱炎性反应,来抑制椎间盘组织细胞凋亡,改善椎间盘退变。

关键词: 二甲双胍, 腰椎间盘退变, 椎间盘组织, 自噬, 凋亡

Abstract: Objective To investigate the impacts of metformin on autophagy and inflammation of intervertebral disc tissue in rabbits, so as to preliminarily explore the molecular mechanism of its anti-intervertebral disc degeneration. Methods The rabbits were diveded into: sham operation group, model group, metformin group, autophagy inhibitor group and metformin + autophagy inhibitor group, with 10 rabbits in each. The positive expression of autophagy-related protein 7 (Atg7) was measured by immunohistochemical staining; The expression of autophagy-related proteins LC3Ⅱ, Beclin1, lysosome-associated membrane protein 2 (LAMP2), tumor necrosis factor-α (TNF-α), IL-1β, and apoptosis-related protein caspase-8 was measured by Western blot. Results Compared with the model group, the intervertebral disc degeneration of the rabbits in the metformin group was alleviated; The formation of autophagosomes and autolysosomes increased. The expression of autophagy proteins increased; And the expression of inflammation and apoptosis proteins decreased (P<0.05). Autophagy inhibitors could inhibit autophagy, aggra- vate intervertebral disc degeneration, increased the expression of inflammatory and apoptotic proteins, and attenuate the autophagy-enhancing, inflammation and apoptosis-enhancing effects by metformin (P<0.05). Conclusions Metformin may inhibit the apoptosis of intervertebral disc tissue and improve intervertebral disc degeneration by promoting autophagy activation and attenuating inflammatory response.

Key words: metformin, lumbar intervertebral disc degeneration, intervertebral disc tissue, autophagy, apoptosis

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