Limb Remote Ischemic Conditioning Promotes Myelination by Upregulating PTEN/Akt/mTOR Signaling Activities after Chronic Cerebral Hypoperfusion.
Limb Remote Ischemic Conditioning Promotes Myelination by Upregulating PTEN/Akt/mTOR Signaling Activities after Chronic Cerebral Hypoperfusion.
复制标题
慢性脑灌注不足后肢体远程缺血调节通过上调 PTEN/Akt/mTOR 信号活动促进髓鞘形成
DOI：
10.14336/ad.2016.1227
复制
发表时间：
2017-07
影响因子：
7.4
通讯作者：
Ji X
中科院分区：
文献类型：
--
作者：
Li X;Ren C;Li S;Han R;Gao J;Huang Q;Jin K;Luo Y;Ji X
肢体远端缺血预处理（LRIC）已被证明是缺血后白色病变的一种有前途的神经保护方法，但其保护慢性脑低灌注损伤的机制仍不清楚。在此，我们研究了LRIC是否通过激活大鼠慢性低灌注模型中的PI 3 K/Akt/mTOR信号通路促进髓鞘生长。30例成年雄性Sprague道利行永久性双颈动脉（2 VO）手术，术后3d行肢体缺血预处理。治疗4周后测定认知功能、少突胶质细胞计数、髓鞘密度、凋亡和增殖活性以及PTEN/Akt/mTOR信号传导活性。结果发现，LRIC可显著抑制慢性脑低灌注后4周的少突胶质细胞凋亡（p<0.05），促进胼胝体髓鞘形成（p<0.01），改善空间学习障碍（p<0.05）。LRIC对胼胝体少突胶质细胞增殖沿着脱髓鞘无明显影响（p>0.05）。Western blot分析显示LRIC上调了胼胝体中的PTEN/Akt/mTOR信号转导活性（p<0.05）。结果提示LRIC通过激活PTEN/Akt/mTOR信号通路对慢性脑低灌注后白色损伤发挥神经保护作用。
Limb Remote ischemic conditioning (LRIC) has been proved to be a promising neuroprotective method in white matter lesions after ischemia; however, its mechanism underlying protection after chronic cerebral hypoperfusion remains largely unknown. Here, we investigated whether LRIC promoted myelin growth by activating PI3K/Akt/mTOR signal pathway in a rat chronic hypoperfusion model. Thirty adult male Sprague Dawley underwent permanent double carotid artery (2VO), and limb remote ischemic conditioning was applied for 3 days after the 2VO surgery. Cognitive function, oligodendrocyte counts, myelin density, apoptosis and proliferation activity, as well as PTEN/Akt/mTOR signaling activity were determined 4 weeks after treatment. We found that LRIC significantly inhibited oligodendrocytes apoptosis (p<0.05), promoted myelination (p<0.01) in the corpus callosum and improved spatial learning impairment (p<0.05) at 4 weeks after chronic cerebral hypoperfusion. Oligodendrocytes proliferation, along with demyelination, in corpus callosum were not obviously affected by LRIC (p>0.05). Western blot analysis indicated that LRIC upregulated PTEN/Akt/mTOR signaling activities in corpus callosum (p<0.05). Our results suggest that LRIC exerts neuroprotective effect on white matter injuries through activating PTEN/Akt/mTOR signaling pathway after chronic cerebral hypoperfusion.