The protective role of 5-hydroxymethyl-2-furfural (5-HMF) against acute hypobaric hypoxia
The protective role of 5-hydroxymethyl-2-furfural (5-HMF) against acute hypobaric hypoxia
复制标题
5-羟甲基-2-糠醛（5-HMF）对急性低压缺氧的保护作用
DOI：
10.1007/s12192-011-0264-8
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发表时间：
2011-09-01
影响因子：
3.8
通讯作者：
Fan, Ming
中科院分区：
文献类型：
--
作者：
Li, Ming-Ming;Wu, Li-Ying;Fan, Ming
我们的前期研究表明5-羟甲基糠醛（5-HMF）预处理可通过p-ERK介导的途径对体外缺氧损伤产生保护作用。5-HMF在体内对缺氧的保护作用是否有效尚不清楚。本研究旨在以昆明种小鼠为动物模型，验证5-羟甲基糠醛在急性低压缺氧中的作用，并进一步探讨其作用机制。采用5-HMF预处理1h和不预处理1h的小鼠在急性低压缺氧条件下暴露6 h，观察小鼠的存活时间、存活率、血脑屏障（BBB）通透性、海马和皮质组织学变化以及丝裂原活化蛋白激酶（ERK、JNK和p38）磷酸化水平。结果表明，5-HMF能显著延长小鼠的存活时间，提高小鼠的存活率。5-HMF预处理可显著降低急性低压缺氧引起的血脑屏障通透性（P < 0.01）。5-HMF预处理可减轻缺氧6 h所致的海马和皮层细胞损伤程度，尤其是海马CA 1区。5-HMF对急性低压缺氧的保护作用可能与ERK的激活有关，而与JNK和p38的激活无关。总之，5-HMF可增强小鼠的生存能力，减轻急性缺氧对脑的损伤，这可能与其对BBB和p-ERK的影响有关。
Our previous study showed that pretreatment with 5-hydroxymethyl-2-furfural (5-HMF) led to protection against hypoxic injury via a p-ERK-mediated pathway in vitro. Whether the protection of 5-HMF against hypoxia is effective in vivo is unknown. The present study is aimed to verify the role of 5-HMF in acute hypobaric hypoxia using Kunming mice as an in vivo model and further investigate the underlying mechanisms. Mice pretreated with or without 5-HMF for 1 h were exposed to acute hypobaric hypoxic condition for 6 h and then the survival time, the survival rate, the permeability of blood-brain barrier (BBB), the histological analysis in hippocampus and cortex, and the phosphorylation level of mitogen-activated protein kinases (ERK, JNK, and p38) were investigated. The results showed that 5-HMF significantly increased the survival time and the survival rate of mice. Accordingly, pretreatment with 5-HMF markedly attenuated acute hypobaric hypoxia-induced permeability of BBB (P < 0.01). In addition, the cellular damage extent of the hippocampus and the cortex induced by hypoxia for 6 h was also attenuated by pretreatment with 5-HMF, especially in the hippocampus CA1 region. Furthermore, the activation of ERK rather than JNK and p38 was involved in the protection of 5-HMF against acute hypobaric hypoxia. In summary, 5-HMF enhanced the survival capability of mice and decreased acute hypoxic damage to the brain, which may be associated with the effects on BBB and p-ERK.