Spontaneous running wheel improves neuroprotection efficacy of ischemic postconditioning in mice following ischemia/reperfusion injury-猫眼课题宝

DOI：

10.32604/biocell.2018.04615

发表时间：

2018

期刊：

Biocell

影响因子：

1.2

通讯作者：

中科院分区：

生物学4区

文献类型：

作者：

H. Ye;Weiwei Wang;Yu Ding;Xiaoli Liu;Jia Wenji;W. Luo;Hui‐Fen Fan;Hong-She Zhou;Jin Wang;Jianlong Ju;Dongming Zhou;T. Bao;Yu-hong Zhu

缺血后处理(IP)对缺血/再灌注(IR)损伤具有保护作用，但其疗效有限。在本研究中，我们假设自发性转轮(RW)可以提高IP对IR的神经保护作用。建立小鼠脑缺血再灌注模型，结果表明，与假手术组相比，脑缺血再灌注组有明显的脑梗塞和神经功能障碍。IR+IP组较IR组脑梗塞和神经功能障碍明显改善。而IR+IP+RW组脑梗塞和神经功能障碍改善明显。原位末端标记法检测显示，IP而不是RW可显著减少IR后的细胞凋亡数。而RW+IP组的凋亡细胞数明显减少。IR组促凋亡因子水平升高，IR+IP+RW组显著降低；抗凋亡因子水平IR组降低，IR+IP+RW组显著升高。IR+IP+RW组与IR+IP组相比，MDA水平进一步降低，SOD水平进一步升高。最后，PI3K抑制剂和STAT3抑制剂均显著加重IR小鼠的脑梗塞和神经功能障碍，并促进细胞凋亡。总之，RW联合IP可减少IR后小鼠的脑梗塞和神经功能障碍，这与通过激活PI3K和STAT3通路而增强的抗细胞凋亡和抗氧化益处有关。

Ischemic postconditioning (IP) has been shown to provide protection for ischemia/reperfusion (IR) injury, but its efficacy is limited. In this study we hypothesized that spontaneous running wheel (RW) could improve neuroprotection efficacy of IP for IR. We established mouse models of IR and showed that compared to Sham group, IR group had obvious brain infract and neurological dysfunction. In IR+IP group, brain infract and neurological dysfunction improved compared to IR group. However, in IR+IP+RW group brain infract and neurological dysfunction improved much better. TUNEL assay showed that IP but not RW significantly reduced the number of apoptotic cells after IR. However, the number of apoptotic cells was significantly reduced in RW+IP group. In addition, the levels of pro-apoptotic factors increased in IR group but significantly reduced in IR+IP+RW group, while the levels of antiapoptotic factors decreased in IR group but significantly increased in IR+IP+RW group. Moreover, in IR+IP+RW group, MDA level was further decreased and SOD level was further increased compared to IR+IP group. Finally, both PI3K inhibitor and STAT3 inhibitor significantly worsened brain infract and neurological dysfunction and promoted apoptosis in IR mice. In conclusion, RW combined with IP reduces brain infract and neurological dysfunction in mice after IR, and this is associated with enhanced anti-apoptotic and anti-oxidant benefits via the activation of PI3K and STAT3 pathways.

Spontaneous running wheel improves neuroprotection efficacy of ischemic postconditioning in mice following ischemia/reperfusion injury

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