Baregamian Naira, Mourot Joshua M, Ballard Amie R, Evers B Mark, Chung Dai H
Department of Surgery, The University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-0353, USA.
Biochem Biophys Res Commun. 2009 Feb 6;379(2):423-7. doi: 10.1016/j.bbrc.2008.11.155. Epub 2008 Dec 27.
Necrotizing enterocolitis (NEC) remains a lethal condition for many premature infants. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma), a member of the nuclear hormone receptor family, has been shown to play a protective role in cellular inflammatory responses; however, its role in NEC is not clearly defined. We sought to examine the expression of PPAR-gamma in the intestine using an ischemia-reperfusion (I/R) model of NEC, and to assess whether PPAR-gamma agonist treatment would ameliorate I/R-induced gut injury. Swiss-Webster mice were randomized to receive sham (control) or I/R injury to the gut induced by transient occlusion of superior mesenteric artery for 45 min with variable periods of reperfusion. I/R injury resulted in early induction of PPAR-gamma expression and activation of NF-kappaB in small intestine. Pretreatment with PPAR-gamma agonist, 15d-PGJ(2), attenuated intestinal NF-kappaB response and I/R-induced gut injury. Activation of PPAR-gamma demonstrated a protective effect on small bowel during I/R-induced gut injury.
坏死性小肠结肠炎(NEC)对许多早产儿来说仍然是一种致命疾病。过氧化物酶体增殖物激活受体γ(PPAR-γ)是核激素受体家族的一员,已被证明在细胞炎症反应中起保护作用;然而,其在NEC中的作用尚未明确界定。我们试图利用NEC的缺血再灌注(I/R)模型检测PPAR-γ在肠道中的表达,并评估PPAR-γ激动剂治疗是否能改善I/R诱导的肠道损伤。将瑞士韦伯斯特小鼠随机分为两组,一组接受假手术(对照),另一组通过暂时阻断肠系膜上动脉45分钟并进行不同时长的再灌注来诱导肠道I/R损伤。I/R损伤导致小肠中PPAR-γ表达的早期诱导和NF-κB的激活。用PPAR-γ激动剂15d-PGJ(2)预处理可减弱肠道NF-κB反应和I/R诱导的肠道损伤。PPAR-γ的激活在I/R诱导的肠道损伤期间对小肠表现出保护作用。