Department of Neurology, Yanbian University Hospital, Yanjin 133000, Jilin, P.R. China.
Department of Oncology, Yanbian University Hospital, Yanjin 133000, Jilin, P.R. China.
Exp Anim. 2022 May 20;71(2):193-203. doi: 10.1538/expanim.21-0137. Epub 2021 Dec 1.
Granulocyte colony-stimulating factor (G-CSF) has been reported to exert a protective effect against secondary brain damage, but the underlying mechanisms remain unknown. We explored the ability of G-CSF to protect the brain from injury in a rat autologous blood-induced model of intracerebral hemorrhage (ICH), with a special focus on the anti-inflammation effect. An ICH was induced in 8-week-old male rats by an infusion of autologous blood, and the rats were then randomly assigned to five treatment groups: sham, ICH, and ICH+ low-dose (25 µg/kg), middle-dose (50 µg/kg), and high-dose (75 µg/kg) G-CSF. We then evaluated the levels of brain inflammation-related genes and proteins. The levels of tumor-necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) mRNA increased between days 1 and 14 post-ICH, with the highest expression on day 3. These changes were rectified by G-CSF in a dose-dependent manner. At day 3 post-injury, an elevation of the nuclear factor-kappa B (NF-κB) p65 protein level and a reduction of the inhibitor of NF-κB alpha (IκBα) protein level were observed; G-CSF treatment exerted a beneficial effect on both protein expressions. The expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins were increased; these changes were rectified by the highest dose of G-CSF. The brain-protecting effects of G-CSF are likely to be attributable, at least in part, to attenuation of the TNF-α, IL-6, iNOS, and COX-2 expressions induced by NF-κB activation in the brain tissues of this autologous blood-induced ICH rat model.
粒细胞集落刺激因子（G-CSF）已被报道具有对抗继发性脑损伤的保护作用，但具体机制尚不清楚。我们研究了 G-CSF 在大鼠自体血诱导的脑出血（ICH）模型中保护大脑免受损伤的能力，特别关注其抗炎作用。通过向 8 周龄雄性大鼠脑内输注自体血诱导 ICH，然后将大鼠随机分为五组：假手术组、ICH 组和 ICH+低剂量（25 µg/kg）、中剂量（50 µg/kg）和高剂量（75 µg/kg）G-CSF 组。然后我们评估了与脑炎症相关的基因和蛋白水平。肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）mRNA 的水平在 ICH 后第 1 天至第 14 天之间增加，在第 3 天表达最高。这些变化呈剂量依赖性被 G-CSF 纠正。在损伤后第 3 天，观察到核因子-κB（NF-κB）p65 蛋白水平升高和 NF-κB 抑制蛋白-α（IκBα）蛋白水平降低；G-CSF 治疗对这两种蛋白表达均有有益作用。诱导型一氧化氮合酶（iNOS）和环氧化酶-2（COX-2）蛋白的表达增加；这些变化被最高剂量的 G-CSF 纠正。G-CSF 的脑保护作用可能至少部分归因于在这种自体血诱导的 ICH 大鼠模型中通过 NF-κB 激活减轻了脑内 TNF-α、IL-6、iNOS 和 COX-2 表达。
