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心脏停搏液组合(腺苷、利多卡因和镁)对缺血性脑卒中模型的神经保护作用。

Neuroprotective Effects of a Cardioplegic Combination (Adenosine, Lidocaine, and Magnesium) in an Ischemic Stroke Model.

机构信息

Department of Anesthesiology, National Taiwan University College of Medicine and National University Hospital, Taipei, Taiwan.

Graduate Institutes of Anatomy and Cell Biology, National Taiwan University College of Medicine, 1 Jen-Ai Road, Section 1, Taipei, 100233, Taiwan.

出版信息

Mol Neurobiol. 2022 Nov;59(11):7045-7055. doi: 10.1007/s12035-022-03020-0. Epub 2022 Sep 8.

Abstract

Adenosine, lidocaine, and magnesium (ALM) are clinically available cardioplegic solutions. We examined the effects of low-dose ALM on ischemic stroke in cell and animal models. Cobalt chloride (CoCl)-treated SH-SY5Y cells were used as a surrogate model to mimic oxygen-glucose deprivation conditions. The cells were incubated with different dilutions of ALM authentic solution (1.0 mM adenosine, 2.0 mM lidocaine, and5 mM MgSO4 in Earle's balanced salt solution). At a concentration of 2.5%, ALM significantly reduced CoCl-induced cell loss. This protective effect persisted even when ALM was administered 1 h after the insult. We used transient middle cerebral artery occlusion to investigate the therapeutic effects of ALM in vivo. Rats were randomly assigned to two groups-the experimental (ALM) and control (saline) groups-and infusion was administered during the ischemia for 1 h. The infarction area was significantly reduced in the ALM group compared with the control group (5.0% ± 2.0% vs. 23.5% ± 5.5%, p = 0.013). Neurological deficits were reduced in the ALM group compared with the control group (modified Longa score: 0 [0-1] vs. 2 [1-2], p = 0.047). This neuroprotective effect was substantiated by a reduction in the levels of various neuronal injury markers in plasma. These results demonstrate the neuroprotective effects of ALM and may provide a new therapeutic strategy for ischemic stroke.

摘要

腺苷、利多卡因和镁(ALM)是临床上可用的心脏停搏液。我们在细胞和动物模型中研究了低剂量 ALM 对缺血性中风的影响。氯化钴(CoCl)处理的 SH-SY5Y 细胞被用作模拟缺氧-葡萄糖剥夺条件的替代模型。将细胞用不同稀释度的 ALM 真实溶液(Earle 平衡盐溶液中的 1.0 mM 腺苷、2.0 mM 利多卡因和 5 mM MgSO4)孵育。在 2.5%的浓度下,ALM 显著减少了 CoCl 诱导的细胞丢失。即使在损伤后 1 小时给予 ALM,这种保护作用仍然存在。我们使用短暂性大脑中动脉闭塞来研究 ALM 在体内的治疗效果。大鼠随机分为两组-实验组(ALM)和对照组(盐水)-并在缺血期间进行 1 小时的输注。与对照组相比,ALM 组的梗死面积明显减小(5.0%±2.0% vs. 23.5%±5.5%,p=0.013)。与对照组相比,ALM 组的神经功能缺损减少(改良 Longa 评分:0[0-1] vs. 2[1-2],p=0.047)。血浆中各种神经元损伤标志物水平的降低证实了这种神经保护作用。这些结果表明了 ALM 的神经保护作用,并可能为缺血性中风提供一种新的治疗策略。

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