Department of Orthopedics, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China.
Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Nantong, 226001, Jiangsu, China.
Neurochem Res. 2018 Aug;43(8):1491-1499. doi: 10.1007/s11064-018-2570-3. Epub 2018 Jun 12.
Spinal cord injury (SCI) is one of the most common and serious condition, which leads to permanent neurological dysfunction and poor prognosis in patients. Hyperglycemia impairs neural functional recovery after SCI resulting in the overproduction of reactive oxygen species (ROS) and inflammatory cytokines. However, the effect of glucose metabolism in the spinal cord after injury remains unclear. AKR1B1, one member of the aldo/keto reductase superfamily, is involved in the energy metabolism of plasm glucose and ROS production. The role of AKR1B1 in cancer cell proliferation and invasion has been confirmed. Meanwhile, Akt, one pivotal transcription factor particularly, is involved in the regulation of cell cycle and ROS-mediated secondary injury in the lesion site. In our study, we established an acute SCI rat model to identify the expression of AKR1B1 and its role in neural recovery processes. Western blotting revealed the expression of AKR1B1 protein was elevated after injury, peaked at 3 days and declined gradually to normal at 14 days. Similar results was illustrated in immunohistochemistry staining of white matter. Double immunofluorescence staining showed AKR1B1 was expressed in glial cells and its expression was significantly increased in proliferative astrocytes during the pathological processes. Further experiments showed AKR1B1 was co-located with Akt protein in GFAP positive cells and immunoprecipitated with Akt in injured spinal cord as well. In summary, the present study demonstrated AKR1B1 played a vital role in astrocytes proliferation through Akt pathway, associated with the metabolism of hyperglycemia induced by SCI.
脊髓损伤 (SCI) 是一种最常见和最严重的疾病，它会导致患者永久性的神经功能障碍和预后不良。高血糖会损害 SCI 后的神经功能恢复，导致活性氧 (ROS) 和炎症细胞因子的过度产生。然而，损伤后脊髓内葡萄糖代谢的影响尚不清楚。AKR1B1 是醛酮还原酶超家族的一员，参与了葡萄糖和 ROS 产生的能量代谢。AKR1B1 在癌细胞增殖和侵袭中的作用已得到证实。同时，Akt 作为一个关键的转录因子，特别参与了细胞周期的调节和损伤部位 ROS 介导的继发性损伤。在我们的研究中，我们建立了一个急性 SCI 大鼠模型，以确定 AKR1B1 的表达及其在神经恢复过程中的作用。Western blot 显示 AKR1B1 蛋白的表达在损伤后升高，在第 3 天达到峰值，然后逐渐下降到 14 天的正常水平。在白质的免疫组织化学染色中也得到了类似的结果。双免疫荧光染色显示 AKR1B1 在神经胶质细胞中表达，在病理过程中增殖的星形胶质细胞中表达显著增加。进一步的实验表明，AKR1B1 与 Akt 蛋白在 GFAP 阳性细胞中共定位，并在损伤的脊髓中与 Akt 免疫沉淀。综上所述，本研究表明 AKR1B1 通过 Akt 通路在星形胶质细胞增殖中发挥重要作用，与 SCI 引起的高血糖代谢有关。
