Hu Xinran, Fukui Yusuke, Feng Tian, Bian Zhihong, Yu Haibo, Morihara Ryuta, Hu Xiao, Bian Yuting, Sun Hongming, Takemoto Mami, Nakano Yumiko, Yunoki Taijun, Abe Koji, Yamashita Toru
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Kita-Ku, Okayama 700-8558, Japan.
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Kita-Ku, Okayama 700-8558, Japan.
J Neurol Sci. 2023 Apr 15;447:120608. doi: 10.1016/j.jns.2023.120608. Epub 2023 Mar 4.
Carnosine (β-alanyl-L-histidine) is a natural dipeptide with multiple neuroprotective properties. Previous studies have advertised that carnosine scavenges free radicals and displays anti-inflammatory activity. However, the underlying mechanism and the efficacies of its pleiotropic effect on prevention remained obscure. In this study, we aimed to investigate the anti-oxidative, anti-inflammative, and anti-pyroptotic effects of carnosine in the transient middle cerebral artery occlusion (tMCAO) mouse model. After a daily pre-treatment of saline or carnosine (1000 mg / kg / day) for 14 days, mice (n = 24) were subjected to tMCAO for 60 min and continuously treated with saline or carnosine for additional 1 and 5 days after reperfusion. The administration of carnosine significantly decreased infarct volume 5 days after the tMCAO (*p < 0.05) and effectively suppressed the expression of 4-HNE, 8-OHdG, Nitrotyrosine 5 days, and RAGE 5 days after tMCAO. Moreover, the expression of IL-1β was also significantly suppressed 5 days after tMCAO. Our present findings demonstrated that carnosine effectively relieves oxidative stress caused by ischemic stroke and significantly attenuates neuroinflammatory responses related to IL-1β, suggesting that carnosine can be a promising therapeutic strategy for ischemic stroke.
肌肽（β-丙氨酰-L-组氨酸）是一种具有多种神经保护特性的天然二肽。先前的研究表明肌肽能清除自由基并具有抗炎活性。然而，其多效性作用对预防的潜在机制和效果仍不清楚。在本研究中，我们旨在研究肌肽在短暂性大脑中动脉闭塞（tMCAO）小鼠模型中的抗氧化、抗炎和抗焦亡作用。在每天用生理盐水或肌肽（1000 mg / kg /天）预处理14天后，将小鼠（n = 24）进行60分钟的tMCAO，并在再灌注后继续用生理盐水或肌肽治疗1天和5天。给予肌肽可显著降低tMCAO后5天的梗死体积（*p < 0.05），并有效抑制tMCAO后5天4-HNE、8-OHdG、硝基酪氨酸和RAGE的表达。此外，tMCAO后5天IL-1β的表达也显著受到抑制。我们目前的研究结果表明，肌肽可有效减轻缺血性中风引起的氧化应激，并显著减轻与IL-1β相关的神经炎症反应，提示肌肽可能是缺血性中风的一种有前景的治疗策略。
