PDF(Pubmed)
Abstract：
Hypoxia-ischaemia (HI) can induce the death of cerebrovascular constituent cells through oxidative stress. Hydrogen is a powerful antioxidant which can activate the antioxidant system. A hypoxia-ischaemia brain damage (HIBD) model was established in 7-day-old SD rats. Rats were treated with different doses of hydrogen-rich water (HRW), and brain pericyte oxidative stress damage, cerebrovascular function and brain tissue damage were assessed. Meanwhile, in vitro-cultured pericytes were subjected to oxygen-glucose deprivation and treated with different concentrations of HRW. Oxidative injury was measured and the molecular mechanism of how HRW alleviated oxidative injury of pericytes was also examined. The results showed that HRW significantly attenuated HI-induced oxidative stress in the brain pericytes of neonatal rats, partly through the Nrf2-HO-1 pathway, further improving cerebrovascular function and reducing brain injury and dysfunction. Furthermore, HRW is superior to a single-cell death inhibitor for apoptosis, ferroptosis, parthanatos, necroptosis and autophagy and can better inhibit HI-induced pericyte death. The liver and kidney functions of rats were not affected by present used HRW dose. This study elucidates the role and mechanism of hydrogen in treating HIBD from the perspective of pericytes, providing new theoretical evidence and mechanistic references for the clinical application of hydrogen in neonatal HIE.
摘要：
缺氧缺血（HI）可通过氧化应激诱导脑血管成分细胞死亡。氢气是一种强大的抗氧化剂，可以激活抗氧化系统。建立7日龄SD大鼠缺氧缺血脑损伤（HIBD）模型。大鼠用不同剂量的富氢水(HRW)处理,和脑周细胞氧化应激损伤，评估脑血管功能和脑组织损伤。同时,对体外培养的周细胞进行氧糖剥夺，并用不同浓度的HRW处理。测量了氧化损伤，并研究了HRW如何减轻周细胞氧化损伤的分子机制。结果显示HRW能显著减弱HI诱导的新生大鼠脑周细胞氧化应激,部分通过Nrf2-HO-1途径，进一步改善脑血管功能，减少脑损伤和功能障碍。此外，HRW优于凋亡的单细胞死亡抑制剂，铁性凋亡,Parthanatos,坏死和自噬能更好地抑制HI诱导的周细胞死亡。目前使用的HRW剂量不影响大鼠的肝肾功能。本研究从周细胞的角度阐明了氢气在治疗HIBD中的作用和机制。为氢气在新生儿HIE中的临床应用提供新的理论依据和机制参考。
