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Astaxanthin alleviates spinal cord ischemia-reperfusion injury via activation of PI3K/Akt/GSK-3β pathway in rats.
Journal of Orthopaedic Surgery and Research ( IF 2.6 ) Pub Date : 2020-07-23 , DOI: 10.1186/s13018-020-01790-8 Jian Fu 1 , Haibin Sun 1 , Haofei Wei 1 , Mingjie Dong 1 , Yongzhe Zhang 1 , Wei Xu 1 , Yanwei Fang 1 , Jianhui Zhao 1
Journal of Orthopaedic Surgery and Research ( IF 2.6 ) Pub Date : 2020-07-23 , DOI: 10.1186/s13018-020-01790-8 Jian Fu 1 , Haibin Sun 1 , Haofei Wei 1 , Mingjie Dong 1 , Yongzhe Zhang 1 , Wei Xu 1 , Yanwei Fang 1 , Jianhui Zhao 1
Affiliation
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.
中文翻译:
虾青素通过激活大鼠的PI3K / Akt /GSK-3β途径减轻脊髓缺血再灌注损伤。
脊髓缺血再灌注损伤(SCII)通常会导致不可改变的神经功能缺损,这可能与氧化应激和炎症引起的细胞凋亡有关。虾青素(AST)是一种强抗氧化剂和抗炎剂,具有多目标神经保护作用。这项研究旨在探讨AST对SCII的潜在治疗作用及其分子机制。建立SCII腹主动脉闭塞40分钟的大鼠模型,以研究AST对SCII恢复的影响。Tarlov评分用于评估神经元功能;HE和TUNEL染色用于观察病变的病理形态。使用商业检测试剂盒测量神经元的氧化应激和炎症。进行流式细胞术以评估线粒体肿胀程度。此外,Western blot法检测PI3K / Akt /GSK-3β途径相关蛋白以及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的恢复,并减轻SCII引起的病理损伤。此外,AST显着增强了抗氧化应激反应并减轻了线粒体肿胀。但是,AST预处理几乎不能抑制SCII后促炎细胞因子的水平。最重要的是,AST激活了p-Akt和p-GSK-3β的表达水平。同时,发现与LY294002(PI3K抑制剂)共同处理可消除上述AST预处理所观察到的保护作用。总体,这些结果表明,AST预处理不仅减轻病理组织损伤,而且还有效地改善了SCII后的神经功能恢复,主要是通过减轻氧化应激反应而不是抑制炎症。AST可能的潜在分子机制可能主要归因于PI3K / Akt /GSK-3β途径的激活。
更新日期:2020-07-23
中文翻译:
虾青素通过激活大鼠的PI3K / Akt /GSK-3β途径减轻脊髓缺血再灌注损伤。
脊髓缺血再灌注损伤(SCII)通常会导致不可改变的神经功能缺损,这可能与氧化应激和炎症引起的细胞凋亡有关。虾青素(AST)是一种强抗氧化剂和抗炎剂,具有多目标神经保护作用。这项研究旨在探讨AST对SCII的潜在治疗作用及其分子机制。建立SCII腹主动脉闭塞40分钟的大鼠模型,以研究AST对SCII恢复的影响。Tarlov评分用于评估神经元功能;HE和TUNEL染色用于观察病变的病理形态。使用商业检测试剂盒测量神经元的氧化应激和炎症。进行流式细胞术以评估线粒体肿胀程度。此外,Western blot法检测PI3K / Akt /GSK-3β途径相关蛋白以及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的恢复,并减轻SCII引起的病理损伤。此外,AST显着增强了抗氧化应激反应并减轻了线粒体肿胀。但是,AST预处理几乎不能抑制SCII后促炎细胞因子的水平。最重要的是,AST激活了p-Akt和p-GSK-3β的表达水平。同时,发现与LY294002(PI3K抑制剂)共同处理可消除上述AST预处理所观察到的保护作用。总体,这些结果表明,AST预处理不仅减轻病理组织损伤,而且还有效地改善了SCII后的神经功能恢复,主要是通过减轻氧化应激反应而不是抑制炎症。AST可能的潜在分子机制可能主要归因于PI3K / Akt /GSK-3β途径的激活。