Department of Orthopaedics, Affiliated Hospital of Nantong University and Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College of Nantong University, 20 Xi-Si Road, Nantong, 226001, Jiangsu, People's Republic of China.
Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College of Nantong University, Nantong, 226001, Jiangsu, People's Republic of China.
Mol Neurobiol. 2016 Nov;53(9):6043-6056. doi: 10.1007/s12035-015-9498-2. Epub 2015 Nov 2.
Traumatic spinal cord injury (SCI) causes tissue loss and associated neurological dysfunction attributable to both mechanical damage and secondary biochemical and physiological responses. Upregulation of cell cycle proteins occurs in both neurons and glia after SCI and may contribute to these changes. Increased cell cycle protein is associated with neuronal and oligodendroglial apoptosis, reactive astrogliosis, glial scar formation, and microglial activation. Here, using lentiviral vectors (LV), we induced the expression of the cyclin-dependent kinase (CDK) inhibitor p27 in the lesioned spinal cord of adult rat. Treatment with LV-p27 significantly reduced the expression of cell cycle proteins and improved functional recovery. In addition, p27 overexpression also reduced lesion volume, decreased astrocytic reactivity, attenuated microglial activation, reduced cell death, and improved the local microenvironment. We suggest that these effects reflect the ability of p27 to inhibit cell cycle pathways. Thus, the present study provides further support for the therapeutic potential of cell cycle inhibitors in the treatment of SCI.
创伤性脊髓损伤（SCI）导致组织损失和相关的神经功能障碍，这归因于机械损伤和继发性生化及生理反应。SCI 后神经元和神经胶质细胞中的细胞周期蛋白上调，可能导致这些变化。细胞周期蛋白的增加与神经元和少突胶质细胞凋亡、反应性星形胶质细胞增生、胶质瘢痕形成和小胶质细胞激活有关。在这里，我们使用慢病毒载体（LV）在成年大鼠损伤的脊髓中诱导细胞周期蛋白依赖性激酶（CDK）抑制剂 p27 的表达。LV-p27 的治疗显著降低了细胞周期蛋白的表达，并改善了功能恢复。此外，p27 的过表达还减少了损伤体积，降低了星形胶质细胞的反应性，减弱了小胶质细胞的激活，减少了细胞死亡，并改善了局部微环境。我们认为这些作用反映了 p27 抑制细胞周期途径的能力。因此，本研究进一步支持细胞周期抑制剂在 SCI 治疗中的治疗潜力。
