Department of Anesthesiology, The First Hospital of China Medical University, Shenyang, Liaoning Province, China.
Int J Neurosci. 2023 Jan;133(1):1-12. doi: 10.1080/00207454.2021.1881089. Epub 2021 Mar 11.
Spinal cord ischemia-reperfusion (I/R) injury is an unresolved complication and its mechanisms are still not completely understood. Here, we studied the neuroprotective effects of dexmedetomidine (DEX) postconditioning against spinal cord I/R injury in rats and explored the possible mechanisms.
In the study, rats were randomly divided into five groups: sham group, I/R group, DEX0.5 group, DEX2.5 group, and DEX5 group. I/R injury was induced in experimental rats; 0.5 μg/kg, 2.5 μg/kg, 5 μg/kg DEX were intravenously injected upon reperfusion respectively. Neurological function, histological assessment, and the disruption of blood-spinal cord barrier (BSCB) were evaluated the BBB scoring, hematoxylin and eosin staining, Evans Blue (EB) extravasation and spinal cord edema, respectively. Neutrophil infiltration was evaluated Myeloperoxidase (MPO) activity. Microglia activation and reactive gliosis was evaluated ionized calcium-binding adapter molecule-1(IBA-1) and glial fibrillary acidic protein (GFAP) immunofluorescence, respectively. The expression of C-X-C motif ligand 13 (CXCL13), C-X-C chemokine receptor type 5(CXCR5), caspase-3 was determined by western blotting. The expression levels of interleukin 6(IL-6), tumor necrosis factor-α(TNF-α), IL-1β were determined by ELISA assay.
DEX postconditioning preserved neurological assessment scores, improved histological assessment scores, attenuated BSCB leakage after spinal cord I/R injury. Neutrophil infiltration, microglia activation and reactive gliosis were also inhibited by DEX postconditioning. The expression of CXCL13, CXCR5, caspase-3, IL-6, TNF-α, IL-1β were reduced by DEX postconditioning.
DEX postconditioning alleviated spinal cord I/R injury, which might be mediated inhibition of neutrophil infiltration, microglia activation, reactive gliosis and CXCL13/CXCR5 axis activation.
脊髓缺血再灌注（I/R）损伤是一个未解决的并发症，其机制仍不完全清楚。在这里，我们研究了右美托咪定（DEX）后处理对大鼠脊髓 I/R 损伤的神经保护作用，并探讨了可能的机制。
在这项研究中，大鼠被随机分为五组：假手术组、I/R 组、DEX0.5 组、DEX2.5 组和 DEX5 组。实验性大鼠诱导 I/R 损伤；再灌注时分别静脉注射 0.5μg/kg、2.5μg/kg、5μg/kg DEX。通过 BBB 评分、苏木精和伊红染色、伊文思蓝（EB）渗出和脊髓水肿分别评估神经功能、组织学评估和血脊髓屏障（BSCB）的破坏。通过髓过氧化物酶（MPO）活性评估中性粒细胞浸润。通过离子钙结合适配器分子-1（IBA-1）和胶质纤维酸性蛋白（GFAP）免疫荧光分别评估小胶质细胞激活和反应性神经胶质增生。通过 Western blot 测定 C-X-C 基序配体 13（CXCL13）、C-X-C 趋化因子受体 5（CXCR5）、半胱天冬酶-3 的表达。通过 ELISA 测定白细胞介素 6（IL-6）、肿瘤坏死因子-α（TNF-α）、IL-1β的表达水平。
DEX 后处理可维持神经学评估评分，改善 I/R 损伤后的组织学评估评分，减轻 BSCB 渗漏。DEX 后处理还抑制了中性粒细胞浸润、小胶质细胞激活和反应性神经胶质增生。DEX 后处理降低了 CXCL13、CXCR5、半胱天冬酶-3、IL-6、TNF-α、IL-1β的表达。
DEX 后处理减轻了脊髓 I/R 损伤，可能是通过抑制中性粒细胞浸润、小胶质细胞激活、反应性神经胶质增生和 CXCL13/CXCR5 轴激活来实现的。
