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乙酰-11-酮-β-乳香酸激活许旺细胞中的 Nrf2/HO-1 信号通路,减少氧化应激,促进坐骨神经损伤修复。

Acetyl-11-Keto-Beta-Boswellic Acid Activates the Nrf2/HO-1 Signaling Pathway in Schwann Cells to Reduce Oxidative Stress and Promote Sciatic Nerve Injury Repair.

机构信息

Department of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang Province, China.

Key Laboratory of Heilongjiang Education Department for Common Animal Disease Prevention and Treatment, Northeast Agricultural University, Harbin, Heilongjiang Province, China.

出版信息

Planta Med. 2023 Dec;89(15):1468-1482. doi: 10.1055/a-2148-7427. Epub 2023 Aug 4.

Abstract

Boswellia is a traditional medicine for bruises and injuries. Its main active ingredient, acetyl-11-keto-beta-boswellic acid, has antioxidant and antiapoptotic effects. In this experiment, we used Sprague-Dawley rats to make a sciatic nerve injury model to detect the transcription factor NF-E2-related factor 2/heme oxygenase 1 signaling pathway and apoptosis, combined with clinical indicators, for testing whether acetyl-11-keto-beta-boswellic acid can reduce oxidative stress and promote sciatic nerve repair. Our results showed that acetyl-11-keto-beta-boswellic acid administration promoted myelin regeneration and functional recovery in the rat sciatic nerve, reduced lipid peroxidation levels, upregulated the expression of various antioxidant enzymes and enhanced enzyme activity, decreased the expression levels of apoptosis-related proteins, and promoted nuclear translocation of the transcription factor NF-E2-related factor 2 protein. studies revealed that acetyl-11-keto-beta-boswellic acid reduced HO-induced reactive oxygen species production, restored mitochondrial membrane potential, upregulated the expression of various antioxidant enzymes, and downregulated apoptosis-related indicators in Schwann cells, and these therapeutic effects of acetyl-11-keto-beta-boswellic acid were reversed after ML385 treatment in Schwann cells. In summary, acetyl-11-keto-beta-boswellic acid alleviates oxidative stress and apoptosis caused by sciatic nerve injury in rats by activating the transcription factor NF-E2-related factor 2/heme oxygenase 1 signaling pathway, promotes the recovery of sciatic nerve function in rats, and is a promising therapeutic agent to promote sciatic nerve repair by alleviating excessive oxidative stress.

摘要

乳香是一种用于治疗瘀伤和损伤的传统药物。其主要活性成分乙酰-11-酮-β-乳香酸具有抗氧化和抗细胞凋亡作用。在这项实验中,我们使用 Sprague-Dawley 大鼠制作坐骨神经损伤模型,以检测转录因子 NF-E2 相关因子 2/血红素加氧酶 1 信号通路和细胞凋亡,并结合临床指标,测试乙酰-11-酮-β-乳香酸是否可以减轻氧化应激并促进坐骨神经修复。我们的结果表明,乙酰-11-酮-β-乳香酸给药促进了大鼠坐骨神经髓鞘再生和功能恢复,降低了脂质过氧化水平,上调了各种抗氧化酶的表达并增强了酶活性,降低了凋亡相关蛋白的表达水平,并促进了转录因子 NF-E2 相关因子 2 蛋白的核转位。研究表明,乙酰-11-酮-β-乳香酸通过降低 HO 诱导的活性氧产生、恢复线粒体膜电位、上调各种抗氧化酶的表达以及下调施万细胞中的凋亡相关指标,减轻坐骨神经损伤引起的氧化应激和细胞凋亡,并且这些乙酰-11-酮-β-乳香酸的治疗作用在施万细胞中用 ML385 处理后被逆转。总之,乙酰-11-酮-β-乳香酸通过激活转录因子 NF-E2 相关因子 2/血红素加氧酶 1 信号通路减轻大鼠坐骨神经损伤引起的氧化应激和细胞凋亡,促进大鼠坐骨神经功能的恢复,是一种有前途的治疗药物,可通过减轻过度氧化应激来促进坐骨神经修复。

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