Zhu Qiankun, He Guizhen, Wang Jie, Wang Yukang, Chen Wei
Department of Parenteral and Enteral Nutrition, Peking Union Medical College Hospital, Peking Union Medical College&Chinese Academy of Medical Sciences, Beijing, 100730, China.
Sci Rep. 2016 Feb 23;6:22044. doi: 10.1038/srep22044.
This experiment was conducted to evaluate whether pretreatment with fenofibrate could mitigate acute lung injury (ALI) in a mice model of intestinal ischemia/reperfusion (I/R). Male C57BL/6 mice were randomly assigned into three groups (n = 6): sham, intestinal I/R + vehicle, and intestinal I/R + fenofibrate. Intestinal I/R was achieved by clamping the superior mesenteric artery. Fenofibrate (100 mg/kg) or equal volume of vehicle was injected intraperitoneally 60 minutes before the ischemia. At the end of experiment, measurement of pathohistological score, inflammatory mediators and other markers were performed. In addition, a 24-hour survival experiment was conducted in intestinal I/R mice treated with fenofibrate or vehicle. The chief results were as anticipated. Pathohistological evaluation indicated that fenofibrate ameliorated the local intestine damage and distant lung injury. Pretreatment with fenofibrate significantly decreased inflammatory factors in both the intestine and the lung. Consistently, renal creatine levels and hepatic ALT levels were significantly decreased in the fenofibrate group. Moreover, serum systemic inflammatory response indicators were significantly alleviated in the fenofibrate group. In addition, fenofibrate administration significantly improved the survival rate. Collectively, our data indicated that pretreatment with fenofibrate prior to ischemia attenuated intestinal I/R injury and ALI.
本实验旨在评估非诺贝特预处理是否能减轻肠缺血/再灌注(I/R)小鼠模型中的急性肺损伤(ALI)。雄性C57BL/6小鼠被随机分为三组(n = 6):假手术组、肠I/R + 赋形剂组和肠I/R + 非诺贝特组。通过夹闭肠系膜上动脉实现肠I/R。在缺血前60分钟腹腔注射非诺贝特(100 mg/kg)或等体积的赋形剂。实验结束时,进行病理组织学评分、炎症介质和其他标志物的测定。此外,对用非诺贝特或赋形剂治疗的肠I/R小鼠进行了24小时生存实验。主要结果符合预期。病理组织学评估表明,非诺贝特改善了局部肠道损伤和远处肺损伤。非诺贝特预处理显著降低了肠道和肺中的炎症因子。同样,非诺贝特组的肾肌酐水平和肝ALT水平显著降低。此外,非诺贝特组的血清全身炎症反应指标显著减轻。此外,给予非诺贝特显著提高了生存率。总体而言,我们的数据表明,缺血前用非诺贝特预处理可减轻肠I/R损伤和ALI。