Mauro Christine R, Tao Ming, Yu Peng, Treviño-Villerreal J Humberto, Longchamp Alban, Kristal Bruce S, Ozaki C Keith, Mitchell James R
Department of Surgery, Brigham and Women's Hospital/Harvard Medical School, Boston, Mass.
Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, Mass.
J Vasc Surg. 2016 Feb;63(2):500-9.e1. doi: 10.1016/j.jvs.2014.07.004. Epub 2014 Aug 8.
Whereas chronic overnutrition is a risk factor for surgical complications, long-term dietary restriction (reduced food intake without malnutrition) protects in preclinical models of surgical stress. Building on the emerging concept that acute preoperative dietary perturbations can affect the body's response to surgical stress, we hypothesized that short-term high-fat diet (HFD) feeding before surgery is detrimental, whereas short-term nutrient/energy restriction before surgery can reverse negative outcomes. We tested this hypothesis in two distinct murine models of vascular surgical injury, ischemia-reperfusion (IR) and intimal hyperplasia (IH).
Short-term overnutrition was achieved by feeding mice a HFD consisting of 60% calories from fat for 2 weeks. Short-term dietary restriction consisted of either 1 week of restricted access to a protein-free diet (protein/energy restriction) or 3 days of water-only fasting immediately before surgery; after surgery, all mice were given ad libitum access to a complete diet. To assess the impact of preoperative nutrition on surgical outcome, mice were challenged in one of two fundamentally distinct surgical injury models: IR injury to either kidney or liver, or a carotid focal stenosis model of IH.
Three days of fasting or 1 week of preoperative protein/energy restriction attenuated IH development measured 28 days after focal carotid stenosis. One week of preoperative protein/energy restriction also reduced plasma urea, creatinine, and damage to the corticomedullary junction after renal IR and decreased aspartate transaminase, alanine transaminase, and hemorrhagic necrosis after hepatic IR. However, exposure to a HFD for 2 weeks before surgery had no significant impact on kidney or hepatic function after IR or IH after focal carotid stenosis.
Short-term dietary restriction immediately before surgery significantly attenuated the vascular wall hyperplastic response and improved IR outcome. The findings suggest plasticity in the body's response to these vascular surgical injuries that can be manipulated by novel yet practical preoperative dietary interventions.
鉴于慢性营养过剩是手术并发症的一个风险因素，长期饮食限制（减少食物摄入量但无营养不良）在手术应激的临床前模型中具有保护作用。基于急性术前饮食扰动可影响机体对手术应激反应这一新兴概念，我们推测术前短期高脂饮食（HFD）有害，而术前短期营养/能量限制可逆转不良结局。我们在两种不同的血管手术损伤小鼠模型，即缺血再灌注（IR）和内膜增生（IH）模型中验证了这一假设。
通过给小鼠喂食含60%脂肪热量的HFD 2周来实现短期营养过剩。短期饮食限制包括术前1周限制获取无蛋白饮食（蛋白质/能量限制）或术前3天仅饮水禁食；术后，所有小鼠可自由获取完整饮食。为评估术前营养对手术结局的影响，在两种根本不同的手术损伤模型之一中对小鼠进行挑战：对肾脏或肝脏的IR损伤，或IH的颈动脉局灶性狭窄模型。
禁食3天或术前1周蛋白质/能量限制可减轻局灶性颈动脉狭窄后28天测量的IH发展。术前1周蛋白质/能量限制还可降低肾IR后血浆尿素、肌酐以及皮质髓质交界处的损伤，并降低肝IR后天冬氨酸转氨酶、丙氨酸转氨酶和出血性坏死。然而，术前2周暴露于HFD对IR或局灶性颈动脉狭窄后IH后的肾脏或肝功能无显著影响。
术前立即进行短期饮食限制可显著减轻血管壁增生反应并改善IR结局。这些发现表明机体对这些血管手术损伤的反应具有可塑性，可通过新颖且实用的术前饮食干预进行调控。
