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分子氢介导糖尿病大鼠卒中后神经修复作用及其机制研究: TLR4/NF-κB 炎症通路。

Molecular Hydrogen Mediates Neurorestorative Effects After Stroke in Diabetic Rats: the TLR4/NF-κB Inflammatory Pathway.

机构信息

Department of Anesthesiology, the Second Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China.

Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, People's Republic of China.

出版信息

J Neuroimmune Pharmacol. 2023 Jun;18(1-2):90-99. doi: 10.1007/s11481-022-10051-w. Epub 2022 Jul 27.

DOI:10.1007/s11481-022-10051-w
PMID:35895245
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10485112/
Abstract

Diabetes is an independent risk factor for stroke and amplifies inflammation. Diabetic stroke is associated with a higher risk of death and worse neural function. The identification of effective anti-inflammatory molecules with translational advantages is particularly important to promote perioperative neurorestorative effects. Applying molecular hydrogen, we measured blood glucose levels before and after middle cerebral artery occlusion (MCAO), 48-h cerebral oedema and infarct volumes, as well as 28-day weight, survival and neurological function. We also measured the levels of TLR4, NF-κB p65, phosphorylated NF-κB p65, catecholamines, acetylcholine and inflammatory factors. All measurements comprehensively showed the positive effect and translational advantage of molecular hydrogen on diabetic stroke. Molecular hydrogen improved the weight, survival and long-term neurological function of rats with diabetic stroke and alleviated changes in blood glucose levels before and after middle cerebral artery occlusion (MCAO), but no difference in circadian rhythm was observed. Molecular hydrogen inhibited the phosphorylation of NF-κB and significantly reduced inflammation. Molecular hydrogen mediates neurorestorative effects after stroke in diabetic rats. The effect is independent of circadian rhythms, indicating translational advantages. The molecular mechanism is related to the TLR4/NF-κB pathway and inflammation. Molecular hydrogen (H) affects outcomes of ischemic stroke with diabetes mellitus (DM).

摘要

糖尿病是中风的独立危险因素,并放大炎症反应。糖尿病性中风与更高的死亡风险和更差的神经功能相关。识别具有转化优势的有效抗炎分子对于促进围手术期神经修复作用尤为重要。我们应用分子氢,测量了大脑中动脉闭塞(MCAO)前后的血糖水平、48 小时脑水肿和梗死体积,以及 28 天的体重、存活率和神经功能。我们还测量了 TLR4、NF-κB p65、磷酸化 NF-κB p65、儿茶酚胺、乙酰胆碱和炎症因子的水平。所有测量结果全面显示了分子氢对糖尿病性中风的积极作用和转化优势。分子氢改善了糖尿病性中风大鼠的体重、存活率和长期神经功能,并减轻了大脑中动脉闭塞前后(MCAO)的血糖变化,但未观察到昼夜节律的差异。分子氢抑制了 NF-κB 的磷酸化,显著减轻了炎症。分子氢介导了糖尿病大鼠中风后的神经修复作用。这种作用独立于昼夜节律,表明具有转化优势。分子机制与 TLR4/NF-κB 途径和炎症有关。分子氢(H)影响糖尿病合并缺血性中风的结局。

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