Jongbloed Franny, de Bruin Ron W F, Pennings Jeroen L A, Payán-Gómez César, van den Engel Sandra, van Oostrom Conny T, de Bruin Alain, Hoeijmakers Jan H J, van Steeg Harry, IJzermans Jan N M, Dollé Martijn E T
Department of Surgery, Laboratory for Experimental Transplantation and Intestinal Surgery (LETIS), Erasmus University Medical Center, Rotterdam, The Netherlands; Laboratory of Health Protection Research, National Institute of Public Health and the Environment, Bilthoven, The Netherlands.
Department of Surgery, Laboratory for Experimental Transplantation and Intestinal Surgery (LETIS), Erasmus University Medical Center, Rotterdam, The Netherlands.
PLoS One. 2014 Jun 24;9(6):e100853. doi: 10.1371/journal.pone.0100853. eCollection 2014.
Ischemia-reperfusion injury (IRI) is inevitable during kidney transplantation leading to oxidative stress and inflammation. We previously reported that preoperative fasting in young-lean male mice protects against IRI. Since patients are generally of older age with morbidities possibly leading to a different response to fasting, we investigated the effects of preoperative fasting on renal IRI in aged-overweight male and female mice. Male and female F1-FVB/C57BL6-hybrid mice, average age 73 weeks weighing 47.2 grams, were randomized to preoperative ad libitum feeding or 3 days fasting, followed by renal IRI. Body weight, kidney function and survival of the animals were monitored until day 28 postoperatively. Kidney histopathology was scored for all animals and gene expression profiles after fasting were analyzed in kidneys of young and aged male mice. Preoperative fasting significantly improved survival after renal IRI in both sexes compared with normal fed mice. Fasted groups had a better kidney function shown by lower serum urea levels after renal IRI. Histopathology showed less acute tubular necrosis and more regeneration in kidneys from fasted mice. A mRNA analysis indicated the involvement of metabolic processes including fatty acid oxidation and retinol metabolism, and the NRF2-mediated stress response. Similar to young-lean, healthy male mice, preoperative fasting protects against renal IRI in aged-overweight mice of both genders. These findings suggest a general protective response of fasting against renal IRI regardless of age, gender, body weight and genetic background. Therefore, fasting could be a non-invasive intervention inducing increased oxidative stress resistance in older and overweight patients as well.
缺血再灌注损伤（IRI）在肾移植过程中不可避免，会导致氧化应激和炎症。我们之前报道过，年轻瘦雄性小鼠术前禁食可预防IRI。由于患者通常年龄较大且患有多种疾病，可能对禁食有不同反应，因此我们研究了术前禁食对老年超重雄性和雌性小鼠肾IRI的影响。将平均年龄73周、体重47.2克的雄性和雌性F1-FVB/C57BL6杂交小鼠随机分为术前自由进食组或禁食3天组，随后进行肾IRI。监测动物的体重、肾功能和生存情况直至术后第28天。对所有动物的肾脏组织病理学进行评分，并分析年轻和老年雄性小鼠禁食后的基因表达谱。与正常进食的小鼠相比，术前禁食显著提高了两性肾IRI后的生存率。IRI后，禁食组的肾功能更好，血清尿素水平更低。组织病理学显示，禁食小鼠肾脏的急性肾小管坏死更少，再生更多。mRNA分析表明，代谢过程包括脂肪酸氧化和视黄醇代谢以及NRF2介导的应激反应参与其中。与年轻瘦的健康雄性小鼠相似，术前禁食可保护老年超重小鼠免受肾IRI的影响。这些发现表明，无论年龄、性别、体重和遗传背景如何，禁食对肾IRI都有普遍的保护作用。因此，禁食可能是一种非侵入性干预措施，也能提高老年和超重患者的氧化应激抵抗力。
