Department of Emergency Surgery, The Second Hospital of Hebei Medical University, No.215 Heping West Road, Shijiazhuang, 050000, Hebei, China.
J Orthop Surg Res. 2020 Jul 23;15(1):275. doi: 10.1186/s13018-020-01790-8.
Ischemia-reperfusion injury of the spinal cord (SCII) often leads to unalterable neurological deficits, which may be associated with apoptosis induced by oxidative stress and inflammation. Astaxanthin (AST) is a strong antioxidant and anti-inflammatory agent with multitarget neuroprotective effects. This study aimed to investigate the potential therapeutic effects of AST for SCII and the molecular mechanism.
Rat models of SCII with abdominal aortic occlusion for 40 min were carried out to investigate the effects of AST on the recovery of SCII. Tarlov's scores were used to assess the neuronal function; HE and TUNEL staining were used to observe the pathological morphology of lesions. Neuron oxidative stress and inflammation were measured using commercial detection kits. Flow cytometry was conducted to assess the mitochondrial swelling degree. Besides, Western blot assay was used to detect the expression of PI3K/Akt/GSK-3β pathway-related proteins, as well as NOX2 and NLRP3 proteins.
The results demonstrated that AST pretreatment promoted the hind limb motor function recovery and alleviated the pathological damage induced by SCII. Moreover, AST significantly enhanced the antioxidative stress response and attenuated mitochondrial swelling. However, AST pretreatment hardly inhibited the levels of proinflammatory cytokines after SCII. Most importantly, AST activated p-Akt and p-GSK-3β expression levels. Meanwhile, cotreatment with LY294002 (a PI3K inhibitor) was found to abolish the above protective effects observed with the AST pretreatment.
Overall, these results suggest that AST pretreatment not only mitigates pathological tissue damage but also effectively improves neural functional recovery following SCII, primarily by alleviating oxidative stress but not inhibiting inflammation. A possible underlying molecular mechanism of AST may be mainly attributed to the activation of PI3K/Akt/GSK-3β pathway.
脊髓缺血再灌注损伤（SCII）常导致不可逆转的神经功能缺损，这可能与氧化应激和炎症诱导的细胞凋亡有关。虾青素（AST）是一种具有抗氧化和抗炎作用的强抗氧化剂，具有多靶点神经保护作用。本研究旨在探讨 AST 对 SCII 的潜在治疗作用及其分子机制。
采用腹主动脉夹闭 40min 建立大鼠 SCII 模型，观察 AST 对 SCII 恢复的影响。Tarlov 评分评估神经元功能；HE 和 TUNEL 染色观察病变的病理形态。采用商业检测试剂盒检测神经元氧化应激和炎症。流式细胞术评估线粒体肿胀程度。此外，Western blot 检测 PI3K/Akt/GSK-3β 通路相关蛋白以及 NOX2 和 NLRP3 蛋白的表达。
结果表明，AST 预处理可促进后肢运动功能恢复，减轻 SCII 引起的病理损伤。此外，AST 显著增强了抗氧化应激反应，减轻了线粒体肿胀。然而，AST 预处理对 SCII 后促炎细胞因子水平几乎没有抑制作用。最重要的是，AST 激活了 p-Akt 和 p-GSK-3β 的表达水平。同时，LY294002（PI3K 抑制剂）共处理发现，AST 预处理观察到的上述保护作用被消除。
综上所述，AST 预处理不仅减轻了病理组织损伤，而且有效改善了 SCII 后的神经功能恢复，主要通过减轻氧化应激而不是抑制炎症。AST 的一个可能的潜在分子机制主要归因于 PI3K/Akt/GSK-3β 通路的激活。
