HB-EGF protects the lungs after intestinal ischemia/reperfusion injury.

HB-EGF protects the lungs after intestinal ischemia/reperfusion injury.
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DOI:
10.1016/j.jss.2010.03.062
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发表时间:
2010-09
期刊:
The Journal of surgical research
影响因子:
--
通讯作者:
Besner GE
Besner GE
中科院分区:
其他
文献类型:
--
作者:
James IA;Chen CL;Huang G;Zhang HY;Velten M;Besner GE

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急性呼吸窘迫综合征仍然是危重患者发病和死亡的主要原因。肝素结合 EGF 样生长因子 (HB-EGF) 是一种生物活性蛋白,可作为肠道细胞保护剂。我们之前已经在几种不同的肠道损伤动物模型中证明 HB-EGF 可以保护肠道免受损伤。在当前的研究中,我们研究了 HB-EGF 在肠缺血/再灌注 (I/R) 后保护肺部免受远程器官损伤的能力。小鼠被随机分配到以下一组:1)假手术; 2) 假手术 + HB-EGF(1200 µg/kg,0.6 mL,在识别出肠系膜上动脉后立即在空肠-回肠交界处进行腔内注射); 3)肠系膜上动脉闭塞45分钟,然后再灌注6小时(I/R);或 4) 血管闭塞后 15 分钟施用 I/R+HB-EGF(1200 µg/kg,0.6 mL)。急性肺损伤的严重程度通过组织学、形态测量分析和侵入性肺功能测试来确定。使用Kaplan-Meier分析评估动物存活率。与假手术动物相比,遭受肠道 I/R 损伤的小鼠显示出急性肺损伤的组织学和功能证据,并且存活率降低。与用 HB-EGF (I/R + HB-EGF) 治疗的小鼠相比,I/R 组的急性肺损伤更严重,存活率更低。我们的结果表明,HB-EGF 可减轻小鼠肠道 I/R 后急性肺损伤的严重程度。这些数据表明,HB-EGF可能是一种潜在的新型全身抗炎剂,用于预防肠道损伤后的全身炎症反应综合征(SIRS)。
Acute respiratory distress syndrome continues to be a major source of morbidity and mortality in critically-ill patients. Heparin binding EGF-like growth factor (HB-EGF) is a biologically active protein that acts as an intestinal cytoprotective agent. We have previously demonstrated that HB-EGF protects the intestines from injury in several different animal models of intestinal injury. In the current study, we investigated the ability of HB-EGF to protect the lungs from remote organ injury after intestinal ischemia/reperfusion (I/R). Mice were randomly assigned to one of the following groups: 1) sham-operated; 2) sham + HB-EGF (1200 µg/kg in 0.6 mL administered by intra-luminal injection at the jejuno-ileal junction immediately after identification of the superior mesenteric artery); 3) superior mesenteric artery occlusion for 45 min followed by reperfusion for 6 h (I/R); or 4) I/R+HB-EGF (1200 µg/kg in 0.6 mL) administered 15 min after vascular occlusion. The severity of acute lung injury was determined by histology, morphometric analysis and invasive pulmonary function testing. Animal survival was evaluated using Kaplan-Meier analysis. Mice subjected to intestinal I/R injury showed histological and functional evidence of acute lung injury and decreased survival compared to sham-operated animals. Compared to mice treated with HB-EGF (I/R + HB-EGF), the I/R group had more severe acute lung injury, and decreased survival. Our results demonstrate that HB-EGF reduces the severity of acute lung injury after intestinal I/R in mice. These data demonstrate that HB-EGF may be a potential novel systemic anti-inflammatory agent for the prevention of the systemic inflammatory response syndrome (SIRS) after intestinal injury.
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