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二甲双胍可减轻铁死亡并促进脊髓损伤的功能恢复。

Metformin Attenuates Ferroptosis and Promotes Functional Recovery of Spinal Cord Injury.

机构信息

Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People's Republic of China.

Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People's Republic of China.

出版信息

World Neurosurg. 2022 Nov;167:e929-e939. doi: 10.1016/j.wneu.2022.08.121. Epub 2022 Sep 2.

Abstract

BACKGROUND

Ferroptosis is involved in traumatic spinal cord injury (SCI), and its inhibition may improve functional recovery after traumatic SCI. This study investigated whether metformin (Met) can have a neuroprotective effect in SCI repair by inhibiting ferroptosis.

METHODS

We assessed functional change to determine the long-term effects after intraperitoneal injection of Met in SCI rats with the Basso-Beattie-Bresnahan locomotor rating scale. Malondialdehyde level and relative expression of key proteins, inflammatory cytokines, and nuclear factor E2-related factor 2 signalling molecules were determined in SCI rats and PC12 cells exposed to FeCl solution.

RESULTS

Met treatment decreased the contents of malondialdehyde, regulated the levels of inflammatory factors, activated the nuclear factor E2-related factor 2 signalling pathway, and improved long-term outcomes by ameliorating SCI-induced locomotor deficits. In vitro studies further confirmed the beneficial and antiferroptotic actions of Met partly through activation of nuclear factor E2-related factor 2 signalling.

CONCLUSION

Met can have a neuroprotective effect on SCI repair partly through antiferroptotic effects.

摘要

背景

铁死亡参与创伤性脊髓损伤(SCI),抑制铁死亡可能改善创伤性 SCI 后的功能恢复。本研究探讨了二甲双胍(Met)是否通过抑制铁死亡对 SCI 修复具有神经保护作用。

方法

我们通过 Basso-Beattie-Bresnahan 运动评分量表评估 SCI 大鼠腹腔注射 Met 后的功能变化,以确定其长期影响。用 FeCl 溶液处理 SCI 大鼠和 PC12 细胞,测定丙二醛水平和关键蛋白、炎症因子和核因子 E2 相关因子 2 信号分子的相对表达。

结果

Met 处理降低了丙二醛的含量,调节了炎症因子的水平,激活了核因子 E2 相关因子 2 信号通路,通过改善 SCI 引起的运动功能障碍,改善了长期预后。体外研究进一步证实了 Met 的有益和抗铁死亡作用,部分是通过激活核因子 E2 相关因子 2 信号通路。

结论

Met 对 SCI 修复的神经保护作用部分是通过抗铁死亡作用实现的。

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