p27Kip1 (p27) regulates the cell cycle by inhibiting G1 progression in cells. Several studies have shown conflicting results on the effects of p27 against cell death in various insults. In the present study, we examined the neuroprotective effects of p27 against H2O2-induced oxidative stress in NSC34 cells and against spinal cord ischemia-induced neuronal damage in rabbits. To promote delivery into NSC34 cells and motor neurons in the spinal cord, Tat-p27 fusion protein and its control protein (Control-p27) were synthesized with or without Tat peptide, respectively. Tat-p27, but not Control-27, was efficiently introduced into NSC34 cells in a concentration- and time-dependent manner, and the protein was detected in the cytoplasm. Tat-p27 showed neuroprotective effects against oxidative stress induced by H2O2 treatment and reduced the formation of reactive oxygen species, DNA fragmentation, and lipid peroxidation in NSC34 cells. Tat-p27, but not Control-p27, ameliorated ischemia-induced neurological deficits and cell damage in the rabbit spinal cord. In addition, Tat-p27 treatment reduced the expression of α-synuclein, activation of microglia, and release of pro-inflammatory cytokines such as interleukin-1β and tumor necrosis factor-α in the spinal cord. Taken together, these results suggest that Tat-p27 inhibits neuronal damage by decreasing oxidative stress, α-synuclein expression, and inflammatory responses after ischemia.

中文翻译：

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Tat-p27 改善神经元损伤，减少脊髓缺血后运动神经元的 α-突触核蛋白和炎症反应。

p27Kip1 (p27) 通过抑制细胞中的 G1 期进程来调节细胞周期。多项研究显示，p27 在各种损伤中对抗细胞死亡的作用存在相互矛盾的结果。在本研究中，我们检查了 p27 对 H2O2 诱导的 NSC34 细胞氧化应激和兔脊髓缺血诱导的神经元损伤的神经保护作用。为了促进递送到脊髓中的 NSC34 细胞和运动神经元中，分别在有或没有 Tat 肽的情况下合成了 Tat-p27 融合蛋白及其对照蛋白 (Control-p27)。Tat-p27（而非 Control-27）以浓度和时间依赖性方式有效引入 NSC34 细胞，并在细胞质中检测到该蛋白质。Tat-p27 对 H2O2 处理诱导的氧化应激具有神经保护作用，并减少 NSC34 细胞中活性氧的形成、DNA 断裂和脂质过氧化。Tat-p27（而非对照-p27）改善了兔脊髓中缺血引起的神经功能缺损和细胞损伤。此外，Tat-p27 治疗可减少脊髓中 α-突触核蛋白的表达、小胶质细胞的激活以及促炎细胞因子（如白介素-1β 和肿瘤坏死因子-α）的释放。综上所述，这些结果表明 Tat-p27 通过减少氧化应激、α-突触核蛋白表达和缺血后的炎症反应来抑制神经元损伤。改善兔脊髓中缺血引起的神经缺陷和细胞损伤。此外，Tat-p27 治疗可减少脊髓中 α-突触核蛋白的表达、小胶质细胞的激活以及促炎细胞因子（如白介素-1β 和肿瘤坏死因子-α）的释放。综上所述，这些结果表明 Tat-p27 通过减少氧化应激、α-突触核蛋白表达和缺血后的炎症反应来抑制神经元损伤。改善兔脊髓中缺血引起的神经缺陷和细胞损伤。此外，Tat-p27 治疗可减少脊髓中 α-突触核蛋白的表达、小胶质细胞的激活以及促炎细胞因子（如白介素-1β 和肿瘤坏死因子-α）的释放。综上所述，这些结果表明 Tat-p27 通过减少氧化应激、α-突触核蛋白表达和缺血后的炎症反应来抑制神经元损伤。