Remote ischemic perconditioning (RIPerC) results in collateral enhancement and a reduction in middle cerebral artery occlusion (MCAO) induced ischemia. RIPerC likely activates multiple metabolic protective mechanisms, including effects on matrix metalloproteinases (MMPs) and protein kinases. Here we explore if RIPerC improves neuroprotection and collateral flow by modifying the activities of MMP-9 and AMPK/e-NOS. Age matched adult male Sprague Dawley rats were subjected to MCAO followed one hour later by RIPerC (3 cycles of 15 min ischemia). Animals were euthanized 24 h post-MCAO. Haematoxylin and Eosin (H&E) staining 24 h post-MCAO revealed a significant (p < 0.02) reduction in the infarction volume in RIPerC treated animals (24.9 ± 5.4%) relative to MCAO controls (42.5 ± 4.2, %). TUNEL staining showed a 42.6% reduction in the apoptotic cells with RIPerC treatment (p < 0.01). Immunoblotting in congruence with RT-PCR and Zymography showed that RIPerC significantly reduced MMP-9 expression and activity in RIPerC + MCAO group compared to MCAO group (218.3 ± 19.1% vs. 148.9 ± 12.05% (p < 0.01). Immunoblotting revealed that RIPerC was associated with a significant 2.5-fold increase in activation of p-AMPK compared to the MCAO group (p < 0.01) which was also associated with a significant increase in the e-NOS activity (p < 0.01). RIPerC resulted in reduction of infarction volume, decreased apoptotic cell death and attenuated MMP-9 activity. This together with the increased activity of p-AMPK and increase in p-eNOS may, in part explain the neuroprotection and sustained increase in blood flow observed with RIPerC following acute stroke.

中文翻译：

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AMPK/e-NOS 信号传导的增加和 MMP-9 的减弱可能有助于局灶性缺血大鼠模型中远程缺血预处理相关的神经保护作用。

远程缺血预处理 (RIPerC) 导致侧支增强和大脑中动脉闭塞 (MCAO) 诱导的缺血减少。RIPerC 可能激活多种代谢保护机制，包括对基质金属蛋白酶 (MMP) 和蛋白激酶的影响。在这里，我们探讨 RIPerC 是否通过改变 MMP-9 和 AMPK/e-NOS 的活性来改善神经保护和侧支血流。年龄匹配的成年雄性 Sprague Dawley 大鼠接受 MCAO，1 小时后接受 RIPerC（3 个循环，15 分钟缺血）。在 MCAO 后 24 小时对动物实施安乐死。MCAO 后 24 小时苏木精和曙红 (H&E) 染色显示，相对于 MCAO 对照 (42.5 ± 4.2, %)，RIPerC 治疗的动物 (24.9 ± 5.4%) 的梗死体积显着减少 (p < 0.02)。TUNEL 染色显示 42。RIPerC 处理使凋亡细胞减少 6% (p < 0.01)。与 RT-PCR 和酶谱相一致的免疫印迹表明，与 MCAO 组相比，RIPerC 显着降低了 RIPerC + MCAO 组中 MMP-9 的表达和活性（218.3 ± 19.1% vs. 148.9 ± 12.05% (p < 0.01)）。免疫印迹显示 RIPerC与 MCAO 组相比，p-AMPK 的活化显着增加 2.5 倍（p < 0.01），这也与 e-NOS 活性的显着增加（p < 0.01）相关。RIPerC 导致梗死体积、凋亡细胞死亡减少和 MMP-9 活性减弱。这与 p-AMPK 活性增加和 p-eNOS 增加一起可能部分解释了 RIPerC 在急性中风后观察到的神经保护作用和血流量持续增加。