Department of Anesthesiology, The First Affiliated Hospital of China Medical University, Nanjingbei Street 155#, Shenyang 110001, Liaoning Province, China.
Department of Anesthesiology, The First Affiliated Hospital of China Medical University, Nanjingbei Street 155#, Shenyang 110001, Liaoning Province, China.
Int Immunopharmacol. 2022 Jul;108:108745. doi: 10.1016/j.intimp.2022.108745. Epub 2022 Apr 11.
Spinal cord ischaemia-reperfusion injury (SCII) induces multiple molecular and cellular changes, resulting in dyskinesia. Recently, it is reported that the p53 network plays a vital role in SCII. However, the roles of the PACT/PRKRA (interferon-inducible double-stranded RNA-dependent protein kinase activator A)-p53 axis in SCII are still unclear. The aim of this study was to elucidate the roles of the PACT-p53 axis in SCII. A Sprague-Dawley rat model of SCII was established by subjecting rats to a 14-min occlusion of the aortic arch. The Tarlov criteria, Western blotting, double immunofluorescence staining, haematoxylin and eosin (HE) staining, and transferase dUTP nick end labelling (TUNEL) assay were performed after SCII. Here, spinal cord ischaemia-reperfusion (SCI) caused hindlimb motor functional deficits as assessed by the Tarlov criteria. The protein expression of PACT was substantially upregulated at 48 h after SCII. Increased PACT fluorescence was mainly localized to neurons. Si-PACT pretreatment improved hindlimb motor function, ameliorated histological changes, and attenuated cell apoptosis after SCII. Si-PACT pretreatment reduced the protein expression of PACT, p53, Caspase-8 and IL-1β and the number of double-labelled PACT and p53. Taken together, inhibiting the aberrant PACT-p53 axis activation by si-PACT pretreatment ameliorates SCI-induced neuroapoptosis and neuroinflammation in rats. Silencing PACT expression is promising new therapeutic strategy for SCII.
脊髓缺血再灌注损伤 (SCII) 诱导多种分子和细胞变化，导致运动障碍。最近，有报道称 p53 网络在 SCII 中发挥着重要作用。然而，PACT/PRKRA（干扰素诱导的双链 RNA 依赖性蛋白激酶激活剂 A）-p53 轴在 SCII 中的作用尚不清楚。本研究旨在阐明 PACT-p53 轴在 SCII 中的作用。通过对大鼠主动脉弓进行 14 分钟的阻塞，建立大鼠 SCII 模型。在 SCII 后进行 Tarlov 标准、Western 印迹、双重免疫荧光染色、苏木精和伊红 (HE) 染色和转移酶 dUTP 缺口末端标记 (TUNEL) 检测。结果显示，脊髓缺血再灌注 (SCI) 导致 Tarlov 标准评估的后肢运动功能障碍。SCI 后 48 小时，PACT 蛋白表达明显上调。荧光强度增加的 PACT 主要定位于神经元。Si-PACT 预处理可改善 SCI 后后肢运动功能，改善组织学变化，减轻细胞凋亡。Si-PACT 预处理可降低 PACT、p53、Caspase-8 和 IL-1β 的蛋白表达以及 PACT 和 p53 的双标记细胞数量。综上所述，通过 Si-PACT 预处理抑制异常的 PACT-p53 轴激活可改善大鼠 SCI 诱导的神经细胞凋亡和神经炎症。沉默 PACT 表达是治疗 SCII 的一种有前途的新策略。
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