Ueno Chikara, Fukatsu Kazuhiko, Maeshima Yoshinori, Moriya Tomoyuki, Shinto Eiji, Hara Etsuko, Nagayoshi Hidetoshi, Hiraide Hoshio, Mochizuki Hidetaka
Department of Surgery I, Division of Basic Traumatology, Research Institute, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.
JPEN J Parenter Enteral Nutr. 2005 Sep-Oct;29(5):345-51; discussion 351-2. doi: 10.1177/0148607105029005345.
Gut ischemia-reperfusion (gut I/R) accompanying severe surgical insults leads to neutrophil-mediated injury and is regarded as a triggering event in early multiple-organ failure. Our previous study demonstrated dietary restriction to down-regulate leukocyte activation. Therefore, we hypothesized dietary restriction might be beneficial in terms of surviving I/R. We also evaluated leukocyte activation and the level of organ glutathione, an antioxidative substance.
Institute of Cancer Research mice received chow, 170 (ad libitum), 119 (MR: mild restriction) or 68 (SR: severe restriction) g/kg per day for 7 days. Exp. 1: The mice (n = 59) underwent 15 or 45 minutes of gut ischemia and survival was observed. Exp. 2: The mice (n = 73) were killed before or 60 or 120 minutes after 15-minute ischemia. Reactive oxygen intermediate (ROI) production by circulating myeloid cells and CD11b expression was determined. Some mice were assessed for nuclear factor kappa B (NFkappaB) activation. Glutathione levels were measured in some of the small intestine and liver samples from each group.
Dietary restriction decreased survival. Circulating myeloid cell priming and activation, in terms of ROI production and CD11b expression, were enhanced in the ad libitum group but not in the restricted groups. NFkappaB was activated only in the ad libitum group. Gut and hepatic glutathione levels were lower in the SR than in the ad libitum group. Dietary restriction caused histologic damages in gut, liver, and lung 120 minutes after reperfusion.
Dietary restriction blunts leukocyte priming and activation after gut ischemic insult but worsens the outcome by, at least in part, decreasing antioxidative activities. Clinically, nutrition replenishment may be required to improve the outcome of gut hypoperfusion.
严重手术创伤伴随的肠道缺血再灌注（肠道I/R）会导致中性粒细胞介导的损伤，被视为早期多器官功能衰竭的触发事件。我们之前的研究表明饮食限制可下调白细胞活化。因此，我们推测饮食限制可能对I/R存活有益。我们还评估了白细胞活化及器官谷胱甘肽（一种抗氧化物质）水平。
癌症研究所的小鼠分别给予正常饲料、每天170（自由摄食）、119（MR：轻度限制）或68（SR：重度限制）g/kg，持续7天。实验1：小鼠（n = 59）经历15或45分钟的肠道缺血，观察存活率。实验2：小鼠（n = 73）在15分钟缺血前、缺血后60或120分钟处死。测定循环髓系细胞产生的活性氧中间体（ROI）及CD11b表达。部分小鼠评估核因子κB（NFκB）活化情况。每组取部分小肠和肝脏样本测定谷胱甘肽水平。
饮食限制降低了存活率。就ROI产生和CD11b表达而言，自由摄食组循环髓系细胞的预激发和活化增强，而限制组未增强。NFκB仅在自由摄食组活化。SR组肠道和肝脏谷胱甘肽水平低于自由摄食组。再灌注120分钟后，饮食限制导致肠道、肝脏和肺组织学损伤。
饮食限制可减轻肠道缺血损伤后白细胞的预激发和活化，但至少部分通过降低抗氧化活性而使结果恶化。临床上，可能需要补充营养以改善肠道低灌注的结局。
