Department of Anesthesiology, The Affiliated Changzhou NO. 2 People's Hospital of Nanjing Medical University, Changzhou, China.
Cell Cycle. 2022 Feb;21(4):406-415. doi: 10.1080/15384101.2021.2020961. Epub 2022 Jan 5.
Stroke is the most frequent cause of disability in developed countries. A common phenomenon of stroke, cerebral ischemia, is threatening many lives worldwide. In addition, ozone treatment was previously reported to exert functions in relieving brain injury. In the current study, the therapeutic effects of ozone on cerebral ischemia are investigated. A rat model of middle cerebral artery occlusion (MCAO) was established. The brain water content was calculated by weighing brain tissues, and the 2, 3, 5-triphenyltetrazolium chloride staining was performed to measure brain infarction volume in rats. A colorimetric assay was conducted to examine expression levels of malondialdehyde, superoxide dismutase, catalase, and glutathione in the rat hippocampus. Reverse transcription quantitative polymerase-chain reaction and Western blot analyses were employed to evaluate expression levels of Beclin1, LC3B, p62, and critical factors implicated in the NF-κB signaling pathway. We found that ozone significantly improved the survival rate of MCAO model rats, reduced the cerebral water content, and decreased the neurological scores of ischemic rats. Ozone markedly reduced cerebral ischemia-induced infarction in ischemic rats. Ozone decreased MDA levels and increased SOD, catalase, and GSH levels in the hippocampus of rats. Ozone significantly inhibited autophagy by decreasing Beclin1 and LC3B expression and increasing p62 expression. The ozone inactivated the NF-κB signaling pathway by decreasing the protein levels of TLR4, p-IKKβ, p-IKBα, and p-p65. We conclude that ozone treatment alleviates the brain injury in ischemic rats by suppressing autophagy and inactivating the NF-κB signaling pathway.
中风是发达国家最常见的致残原因。脑缺血是中风的一种常见现象，正在威胁着全世界许多人的生命。此外，臭氧治疗以前被报道具有缓解脑损伤的功能。在本研究中，研究了臭氧对脑缺血的治疗作用。建立了大脑中动脉闭塞（MCAO）大鼠模型。通过称重脑组织计算脑水含量，并对大鼠脑梗死体积进行 2,3,5-氯化三苯基四氮唑染色。进行比色法测定大鼠海马组织中丙二醛、超氧化物歧化酶、过氧化氢酶和谷胱甘肽的表达水平。采用逆转录定量聚合酶链反应和 Western blot 分析评估 NF-κB 信号通路中关键因子 Beclin1、LC3B、p62 的表达水平。结果发现，臭氧显著提高了 MCAO 模型大鼠的存活率，降低了脑水含量，降低了缺血性大鼠的神经评分。臭氧显著减少了缺血性大鼠脑缺血引起的梗死。臭氧降低了 MDA 水平，增加了 SOD、过氧化氢酶和 GSH 水平。臭氧通过降低 Beclin1 和 LC3B 的表达和增加 p62 的表达显著抑制自噬。臭氧通过降低 TLR4、p-IKKβ、p-IKBα 和 p-p65 的蛋白水平使 NF-κB 信号通路失活。我们得出结论，臭氧处理通过抑制自噬和使 NF-κB 信号通路失活来减轻缺血性大鼠的脑损伤。
