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