Chen Chunxia, Huang Luying, Nong Zhihuan, Li Yaoxuan, Chen Wan, Huang Jianping, Pan Xiaorong, Wu Guangwei, Lin Yingzhong
Department of Hyperbaric oxygen, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, Guangxi, People's Republic of China.
Department of Respiratory Diseases, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, Guangxi, People's Republic of China.
Neurochem Res. 2017 Apr;42(4):1240-1253. doi: 10.1007/s11064-016-2166-8. Epub 2017 Jan 11.
Our previous study demonstrated that hyperbaric oxygen (HBO) improved cognitive impairments mainly by regulating oxidative stress, inflammatory responses and aging-related gene expression. However, a method for preventing cognitive dysfunction has yet to be developed. In the present study, we explored the protective effects of HBO on the cholinergic system and apoptosis in D-galactose (D-gal)-treated mice. A model of aging was established via systemic intraperitoneal injection of D-gal daily for 8 weeks. HBO was administered during the last 2 weeks of D-gal injection. Our results showed that HBO in D-gal-treated mice significantly improved behavioral performance on the open field test and passive avoidance task. Studies on the potential mechanisms of this effect showed that HBO significantly reduced oxidative stress and blocked the nuclear factor-κB pathway. Moreover, HBO significantly increased the levels of choline acetyltransferase and acetylcholine and decreased the activity of acetylcholinesterase in the hippocampus. Furthermore, HBO markedly increased expression of the anti-apoptosis protein Bcl-2 and glial fibrillary acidic protein meanwhile decreased expression of the pro-apoptosis proteins Bax and caspase-3. Importantly, there was a significant reduction in expression of Aβ-related genes, such as amyloid precursor protein, β-site amyloid cleaving enzyme-1 and cathepsin B mRNA. These decreases were accompanied by significant increases in expression of neprilysin and insulin-degrading enzyme mRNA. Moreover, compared with the Vitamin E group, HBO combined with Vitamin E exhibited significant difference in part of the above mention parameters. These findings suggest that HBO may act as a neuroprotective agent in preventing cognitive impairments.
我们之前的研究表明，高压氧（HBO）主要通过调节氧化应激、炎症反应和衰老相关基因表达来改善认知障碍。然而，尚未开发出预防认知功能障碍的方法。在本研究中，我们探讨了HBO对D-半乳糖（D-gal）处理的小鼠胆碱能系统和细胞凋亡的保护作用。通过每天腹腔注射D-gal，持续8周建立衰老模型。在注射D-gal的最后2周给予HBO。我们的结果表明，HBO对D-gal处理的小鼠在旷场试验和被动回避任务中的行为表现有显著改善。对这种作用潜在机制的研究表明，HBO显著降低了氧化应激并阻断了核因子κB通路。此外，HBO显著提高了海马中胆碱乙酰转移酶和乙酰胆碱的水平，并降低了乙酰胆碱酯酶的活性。此外，HBO显著增加了抗凋亡蛋白Bcl-2和胶质纤维酸性蛋白的表达，同时降低了促凋亡蛋白Bax和caspase-3的表达。重要的是，与淀粉样前体蛋白、β-位点淀粉样蛋白裂解酶-1和组织蛋白酶B mRNA等Aβ相关基因的表达显著降低。这些降低伴随着中性内肽酶和胰岛素降解酶mRNA表达的显著增加。此外，与维生素E组相比，HBO联合维生素E在上述部分参数上表现出显著差异。这些发现表明，HBO可能作为一种神经保护剂预防认知障碍。
