Objectives

We aimed to investigate the protective effects of cyclosporin A (CsA) against ischemia-reperfusion (I/R) damage in a mouse ischemia model and the possible underlying mechanism.

Methods

Mice were divided equally into five groups: Sham, I/R, Vehicle, I/R plus CsA (10 mg/kg), and I/R plus CsA (20 mg/kg). Nerve function scores, infarct volume, brain water content, and Evans blue (EB) leakage were evaluated, and western blotting was performed to analyze the changes in CypA, p-Akt, NF-κB, MMP-9, and Claudin-5 expression.

Results

CsA can attenuate I/R damage in a mouse ischemic stroke model, as indicated by improved neurological function scores and decreased infarct volume, brain water content, and EB leakage. Additionally, high-dose CsA showed better protective effects than low-dose. The molecular mechanisms underlying the effects of CsA were explored, and it was found that CsA could inhibit the increase in CypA, p-Akt, NF-κB, and MMP-9 protein expression after middle cerebral artery occlusion, while Claudin-5 expression was decreased.

Discussion

CsA showed potential as a neuroprotective drug for the treatment of ischemic stroke patients; besides interfering with the typical NF-κB signaling pathway, the Akt pathway may also be involved in the effects of CsA.

中文翻译：

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在缺血性中风的小鼠模型中环孢菌素a对缺血-再灌注损伤的作用。

目标

我们旨在研究环孢菌素A（CsA）对小鼠缺血模型中缺血再灌注（I / R）损伤的保护作用及其可能的潜在机制。

方法

将小鼠平均分为五组：假手术，I / R，媒介物，I / R加CsA（10 mg / kg）和I / R加CsA（20 mg / kg）。评价神经功能评分，梗塞体积，脑含水量和伊文思蓝（EB）渗漏，并进行免疫印迹分析CypA，p-Akt，NF-κB，MMP-9和Claudin-5表达的变化。 。

结果

CsA可以减轻小鼠缺血性中风模型中的I / R损伤，如改善的神经功能评分和减少的梗死体积，脑含水量和EB泄漏所表明的。此外，高剂量的CsA显示出比低剂量更好的保护作用。探索了影响CsA的分子机制，发现CsA抑制大脑中动脉闭塞后CypA，p-Akt，NF-κB和MMP-9蛋白表达的增加，而Claudin-5表达为减少了。

讨论区

CsA具有治疗神经性中风的潜力。除了干扰典型的NF-κB信号传导途径外，Akt途径也可能参与了CsA的作用。