Department of Basic Medicine Science, Medical College of Qinghai University, Xining 810001, China.
Department of Basic Medicine Science, Medical College of Qinghai University, Xining 810001, China.
Eur J Pharmacol. 2018 Jan 5;818:300-305. doi: 10.1016/j.ejphar.2017.10.042. Epub 2017 Oct 26.
This study investigated whether crocin exerted neuroprotective effects against acute hypobaric hypoxia at high altitude in vivo and determined the underlying mechanisms. Male Sprague-Dawley rats were randomly assigned to a normoxic group，a hypoxic group, and three crocin groups at three different doses. The rats were transferred from 50m to 4200m for 3 days after treatment with crocin for 3 days. The learning and memory of the rat were evaluated with the Morris water maze test. Transmission electron microscope (TEM) was used to analyze the changes in the ultrastructure of hippocampal neurons. Peroxisome proliferator-activated receptor-γ co-activator 1α (PGC-1α) and sirtuin-1 (SIRT1) levels were determined using immunohistochemical staining and western blotting. The escape latency of the crocin group was shorter than that of the hypoxic group, while the frequency of the rats reaching the platform was significantly higher in the crocin group. The structures of nerve cells and mitochondria were destroyed in the hypoxic group, but were repaired in the crocin groups. The expressions of PGC-1α and SIRT1 were decreased in the hypoxic group, but were increased in the crocin group. All the effects improved by crocin were dose-dependent. Crocin attenuates acute hypobaric hypoxia-induced cognitive deficits in rats, accompanied by repairing the structures of hippocampal neurons and improving PGC-1α and SIRT1 levels.
本研究旨在探讨西红花苷（一种藏红花提取物）是否对高原低氧环境下的急性缺氧具有神经保护作用，并探讨其潜在机制。雄性 Sprague-Dawley 大鼠随机分为常氧组、缺氧组和三个西红花苷剂量组。各组大鼠在连续 3 天给予西红花苷处理后，从 50m 海拔转移到 4200m 海拔，持续 3 天。采用 Morris 水迷宫试验评估大鼠的学习和记忆能力。通过透射电子显微镜（TEM）分析海马神经元超微结构的变化。采用免疫组织化学染色和 Western blot 检测过氧化物酶体增殖物激活受体γ共激活因子 1α（PGC-1α）和沉默调节蛋白 1（SIRT1）的水平。与缺氧组相比，西红花苷组的逃避潜伏期较短，而到达平台的频率明显更高。缺氧组神经细胞和线粒体结构受损，但西红花苷组得到修复。缺氧组的 PGC-1α 和 SIRT1 表达降低，而西红花苷组表达增加。西红花苷的所有作用均呈剂量依赖性。西红花苷可减轻急性低氧诱导的大鼠认知功能障碍，同时修复海马神经元结构，提高 PGC-1α 和 SIRT1 水平。
