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原花青素通过抑制铁死亡促进脊髓损伤功能恢复。

Proanthocyanidin promotes functional recovery of spinal cord injury via inhibiting ferroptosis.

机构信息

Emergency Department, Jiangyin People's Hospital, Jiangsu, China.

Department of General Surgery, Affiliated Hospital of Jiangsu University, Jiangsu, China.

出版信息

J Chem Neuroanat. 2020 Sep;107:101807. doi: 10.1016/j.jchemneu.2020.101807. Epub 2020 May 28.

DOI:10.1016/j.jchemneu.2020.101807
PMID:32474063
Abstract

Improving the microenvironment of lesioned spinal cord to minimize the secondary injury is one important strategy to treat spinal cord injury (SCI). The ensuing hemorrhage after SCI has tight connection with ferroptosis. This study investigated the effects of proanthocyanidins (PACs) on SCI repair and the underlying mechanisms. Adult female mice were divided into four groups, including sham, SCI, PACs5 and PACs10 (i.p. 5 and 10 mg/kg PACs after SCI respectively). The impacts of SCI and PACs treatment on redox parameters (iron contents, TBARS, GSH, and GPX activities) and ferroptosis essential factors such as ACSL4, LPCAT3, Alox15B, Nrf2, HO-1, GPX4 were investigated. The results demonstrated that PACs treatment significantly decreased the levels of iron, TBARS, ACSL4, and Alox15B, while increased the levels of GSH, GPX4, Nrf2, and HO-1 in traumatic spinal cords. Above all, PACs improved the locomotive function of SCI mice. These results suggest that PACs might be potential therapeutics for SCI repair by inhibiting ferroptosis in SCI.

摘要

改善损伤脊髓的微环境以最小化继发性损伤是治疗脊髓损伤 (SCI) 的一个重要策略。SCI 后的出血与铁死亡密切相关。本研究探讨了原花青素 (PACs) 对 SCI 修复的影响及其潜在机制。成年雌性小鼠分为四组,包括假手术组、SCI 组、PACs5 组和 PACs10 组(SCI 后分别腹腔注射 5 和 10mg/kg PACs)。研究了 SCI 和 PACs 处理对氧化还原参数(铁含量、TBARS、GSH 和 GPX 活性)和铁死亡必需因素(ACSL4、LPCAT3、Alox15B、Nrf2、HO-1 和 GPX4)的影响。结果表明,PACs 处理显著降低了创伤性脊髓中的铁、TBARS、ACSL4 和 Alox15B 水平,而增加了 GSH、GPX4、Nrf2 和 HO-1 的水平。最重要的是,PACs 改善了 SCI 小鼠的运动功能。这些结果表明,PACs 通过抑制 SCI 中的铁死亡可能成为治疗 SCI 的潜在疗法。

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