Department of Anesthesia, People's Liberation Army The General Hospital of Western Theater Command, Chengdu, Sichuan 610083, China.
School of Electrical Engineering and Information, Southwest Petroleum University, Chengdu, Sichuan 610083, China.
Neurosci Lett. 2023 Jul 27;810:137359. doi: 10.1016/j.neulet.2023.137359. Epub 2023 Jun 24.
Spinal cord ischemia-reperfusion injury (SCII) is usually caused by spinal surgery, often leading to severe neurological deficits. The ubiquitin-specific protease 18 (USP18) plays a significant role in neurological diseases.
The present study was designed to assess the effects and mechanisms of USP18 on SCII.
By inducing transient aortic occlusion and subsequent reperfusion, a rat model of SCII was successfully established. The Basso-Beattie-Bresnahan scores, the inclined plane test, and hematoxylin and eosin (HE) were used to measure locomotor activity and histological changes in the injured spinal cords. Moreover, the SCII cell model was established using PC12 cells under oxygen-glucose deprivation and reoxygenation (OGD/R). Proinflammatory factors (TNF-α, IL-6, and INF-α) were examined using an ELISA kit. Cell apoptosis was assessed by Annexin V-FITC/PI double-staining and TUNEL assays. Western blot was used to detect the expression levels of proteins related to apoptosis and autophagy.
USP18 expression was decreasedin vivo and in vitro SCII models. The upregulation of USP18 ameliorated hind limbs' motor function, inhibiting inflammation and apoptosis after SCII in rats. USP18 overexpression in vitro may protect PC12 cells from OGD/R-induced damage by modulating inflammatory responses and apoptosis. Moreover, Overexpression of USP18 enhanced autophagy to inhibit cell apoptosis induced by SCII in vivo and in vitro.
In summary, USP18 overexpression protects against SCII via regulating autophagy.
脊髓缺血再灌注损伤（SCII）通常由脊髓手术引起，常导致严重的神经功能缺损。泛素特异性蛋白酶 18（USP18）在神经疾病中发挥重要作用。
本研究旨在评估 USP18 对 SCII 的影响及其机制。
通过诱导短暂性主动脉闭塞和随后的再灌注，成功建立了大鼠 SCII 模型。Basso-Beattie-Bresnahan 评分、斜板试验和苏木精-伊红（HE）染色用于评估损伤脊髓的运动活动和组织学变化。此外，采用氧葡萄糖剥夺和复氧（OGD/R）建立 PC12 细胞 SCII 模型。ELISA 试剂盒检测促炎因子（TNF-α、IL-6 和 INF-α）。通过 Annexin V-FITC/PI 双染和 TUNEL 检测评估细胞凋亡。Western blot 检测与细胞凋亡和自噬相关的蛋白表达水平。
体内和体外 SCII 模型中 USP18 的表达均降低。USP18 的上调改善了大鼠 SCII 后后肢运动功能，抑制了炎症和细胞凋亡。体外过表达 USP18 可能通过调节炎症反应和细胞凋亡来保护 PC12 细胞免受 OGD/R 诱导的损伤。此外，过表达 USP18 增强自噬以抑制体内和体外 SCII 诱导的细胞凋亡。
总之，USP18 的过表达通过调节自噬来保护 SCII。
