Department of Cardiovascular Surgery, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, People's Republic of China.
Int J Mol Med. 2013 Jun;31(6):1367-74. doi: 10.3892/ijmm.2013.1347. Epub 2013 Apr 15.
Intestinal ischemia/reperfusion (I/R) injury is considered to be associated with high morbidity and mortality rates. Osthole, a natural derivative of coumarin, has been shown to exert a variety of pharmacological and therapeutic effects under physiological and pathological conditions. In the present study, to investigate the protective effects of osthole against intestinal I/R injury, various doses of osthole (5, 10, 25 and 50 mg/kg) were pre-administered to mice subjected to intestinal I/R injury. A dose-dependent increase in the survival rate was observed in the osthole-treated mice. Pre-treatment with osthole (50 mg/kg) attenuated the destruction of epithelial cells within the villi induced by intestinal I/R injury, and suppressed oxidative stress, neutrophil infiltration and modulated nitric oxide (NO) levels. Moreover, the increased IκBα phosphorylation and nuclear factor (NF)-κB nuclear translocation induced by I/R injury were significantly decreased following pre-treatment with osthole. Taken together, our data demonstrate that osthole exerts protective effects against intestinal I/R injury in mice by suppressing oxidative stress, neutrophil infiltration and NO levels, partly through the inhibition of NF-κB nuclear translocation. Hence, the findings of the present study provide insight into the mechanisms through which osthole exerts its protective effects against intestinal I/R injury.
肠缺血/再灌注 (I/R) 损伤被认为与高发病率和死亡率有关。蛇床子素是香豆素的天然衍生物,在生理和病理条件下已显示出多种药理和治疗作用。在本研究中,为了研究蛇床子素对肠 I/R 损伤的保护作用,将不同剂量的蛇床子素(5、10、25 和 50mg/kg)预先给予肠 I/R 损伤的小鼠。在蛇床子素处理的小鼠中观察到存活率呈剂量依赖性增加。蛇床子素(50mg/kg)预处理可减轻肠 I/R 损伤引起的绒毛上皮细胞破坏,并抑制氧化应激、中性粒细胞浸润和调节一氧化氮 (NO) 水平。此外,I/R 损伤诱导的 IκBα 磷酸化和核因子 (NF)-κB 核易位明显减少。综上所述,我们的数据表明,蛇床子素通过抑制氧化应激、中性粒细胞浸润和 NO 水平来发挥对小鼠肠 I/R 损伤的保护作用,部分通过抑制 NF-κB 核易位。因此,本研究的结果为蛇床子素发挥对肠 I/R 损伤的保护作用的机制提供了新的见解。