1 Department of Emergency, the Second Hospital of Hebei Medical University , Shijiazhuang, Hebei, China .
2 Key Laboratory of Emergency Medicine of Hebei Province, the Second Hospital of Hebei Medical University , Shijiazhuang, Hebei, China .
J Med Food. 2018 Jan;21(1):13-20. doi: 10.1089/jmf.2017.4021. Epub 2017 Oct 4.
Luteolin (LU) is a widely distributed flavonoid with multitarget effects. The objective of this study was to determine whether LU could reduce the ischemia-reperfusion injury of the spinal cord (SCII) in a rat model. Forty-eight rats were divided into four groups: sham, SCII, SCII+L-LU (50 mg/kg), and SCII+H-LU (100 mg/kg). Abdominal aortic occlusion was carried out for 40 min in all groups. Hindlimb motor functions were evaluated using the Tarlov scoring system. Nissl and terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labeling (TUNEL) staining were used to detect cell survival and apoptosis in the spinal cord. Spinal cord samples were taken for determination of malondialdehyde, xanthine oxidase, superoxide dismutase, and glutathione peroxidase activities. The levels of tumor necrosis factor-α, interleukin (IL)-1β, and IL-18 were assessed using ELISA kits to examine the inflammatory responses in the spinal cord. Western blot analysis was used to examine the expression of nuclear factor erythroid 2-related factor (Nrf2) and nod-like receptor pyrin domain-containing 3 protein (NLRP3) levels. We found that LU pretreatment significantly improved the locomotor function of rats after SCII, increased neuron survival, and inhibited apoptosis in the spinal cord. Furthermore, the oxidative stress and inflammatory response were significantly suppressed upon treatment with LU. Finally, LU upregulated Nrf2 levels and downregulated NLRP3 protein expression in SCII tissues. Thus, LU exhibited a neuroprotective effect following SCII by alleviating oxidative stress and inhibiting inflammatory responses and cell apoptosis. The possible mechanism may be related to the activation of Nrf2 and inhibition of NLRP3 inflammasome pathway.
木犀草素（LU）是一种分布广泛的具有多靶点效应的黄酮类化合物。本研究旨在探讨木犀草素是否能减轻大鼠脊髓缺血再灌注损伤（SCII）。48 只大鼠随机分为假手术组、SCII 组、SCII+L-LU（50mg/kg）组和 SCII+H-LU（100mg/kg）组。所有组均行腹主动脉夹闭 40min。采用 Tarlov 评分系统评估后肢运动功能。Nissl 和末端脱氧核苷酸转移酶介导的 dUTP 生物素缺口末端标记（TUNEL）染色检测脊髓细胞存活和凋亡。取脊髓样本测定丙二醛、黄嘌呤氧化酶、超氧化物歧化酶和谷胱甘肽过氧化物酶活性。采用 ELISA 试剂盒检测脊髓组织中肿瘤坏死因子-α、白细胞介素（IL）-1β和 IL-18 的水平，以评估炎症反应。Western blot 分析检测核因子红细胞 2 相关因子（Nrf2）和核苷酸结合寡聚结构域样受体热蛋白结构域包含蛋白 3（NLRP3）的表达。结果发现，LU 预处理可显著改善 SCII 后大鼠的运动功能，增加神经元存活，抑制脊髓细胞凋亡。此外，LU 治疗可显著抑制氧化应激和炎症反应。最后，LU 上调了 SCII 组织中 Nrf2 水平，下调了 NLRP3 蛋白表达。综上，LU 通过减轻氧化应激、抑制炎症反应和细胞凋亡，对 SCII 发挥神经保护作用。其可能的机制与 Nrf2 激活和 NLRP3 炎症小体途径抑制有关。
