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treadmill 训练通过 JAK2/STAT3 信号通路和减轻细胞凋亡改善脊髓损伤大鼠的神经功能恢复。

Treadmill training improves neural function recovery in rats with spinal cord injury via JAK2/STAT3 signaling pathway and attenuating apoptosis.

机构信息

Department of Hyperbaric Oxygen, Zhujiang Hospital, Southern Medical University, Guangzhou.

Neurology Department, Affiliated Hospital of Guilin Medical University, Guilin Medical University, Guangxi.

出版信息

Neuroreport. 2024 Sep 4;35(13):811-821. doi: 10.1097/WNR.0000000000002062. Epub 2024 Jul 8.

Abstract

To investigate the role of JAK2/STAT3 signaling pathway in neural function recovery in rats with spinal cord injury (SCI) after treadmill training. Sprague-Dawley rats were randomly divided into four groups: (a) sham group; (b) SCI group; (c) SCI+treadmill training group (SCI/TT); and (d) SCI/TT+AG490 group (a JAK2 inhibitor) ( n  = 12). The 12 Sprague-Dawley rats in each group were randomly assigned into 1 st , 3 rd , 7 th , and 14 th  day subgroups. The Basso-Beattie-Bresnahan (BBB) locomotor rating scale was used to assess the spinal cord function, and JAK2, STAT3, and IL-6 protein expressions in the rat spinal cord were evaluated by western blot. The level of cell apoptosis and expressions of apoptotic proteins were evaluated by TUNEL assay and immunohistochemistry, respectively. Rats in the SCI+TT group showed a significantly higher BBB score after SCI compared with the SCI group and the SCI/TT+AG490 group. Mechanistically, the JAK2/STAT3 signal pathway was immediately activated after SCI compared with sham group, and JAK2 and STAT3 were obviously upregulated when treadmill training was performed ( P  < 0.05). Results of TUNEL assay showed that the apoptotic rate in SCI/TT was significantly lower than that in the SCI group and SCI/TT+AG490 group ( P  < 0.05). Besides, the IL-6 expression in the SCI/TT group was significantly attenuated compared with the SCI group ( P  < 0.05). Our results showed that physical treadmill training can enhance activation of JAK2/STAT3 signal pathway and attenuate apoptosis in the injured spinal cord, resulting in better functional recovery. These results underline the importance of synergistic treatment strategies for SCI.

摘要

目的

探讨跑台训练对脊髓损伤(SCI)大鼠神经功能恢复中 JAK2/STAT3 信号通路的作用。

方法

将 Sprague-Dawley 大鼠随机分为 4 组:(a)假手术组;(b)SCI 组;(c)SCI+跑台训练组(SCI/TT);(d)SCI/TT+AG490 组(JAK2 抑制剂)(n=12)。每组 12 只大鼠随机分为 1 天、3 天、7 天和 14 天亚组。采用 Basso-Beattie-Bresnahan(BBB)运动评分量表评估脊髓功能,采用 Western blot 法评估大鼠脊髓 JAK2、STAT3 和 IL-6 蛋白表达。TUNEL 检测和免疫组化分别评估细胞凋亡水平和凋亡蛋白表达。

结果

SCI/TT 组 SCI 后 BBB 评分明显高于 SCI 组和 SCI/TT+AG490 组。与假手术组相比,SCI 后 JAK2/STAT3 信号通路立即被激活,进行跑台训练时 JAK2 和 STAT3 明显上调(P<0.05)。TUNEL 检测结果显示,SCI/TT 组的凋亡率明显低于 SCI 组和 SCI/TT+AG490 组(P<0.05)。此外,SCI/TT 组的 IL-6 表达明显低于 SCI 组(P<0.05)。

结论

跑台训练可以增强 JAK2/STAT3 信号通路的激活,减轻损伤脊髓中的细胞凋亡,从而促进更好的功能恢复。这些结果强调了协同治疗策略对 SCI 的重要性。

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