Department of Surgery, Division of Transplantation, University of California, San Francisco, CA 94143-0648, USA.
J Gastroenterol. 2010 Nov;45(11):1103-10. doi: 10.1007/s00535-010-0262-0. Epub 2010 Jun 15.
Intestinal ischemia can occur from mesenteric artery (MA) occlusion and portal vein (PV) occlusion. The degree and mechanisms of ischemia/reperfusion (I/R) injury in these conditions may differ. Metabolic changes are seen early in I/R. This study compares tissue histology, inflammation, and metabolic response during small bowel I/R due to superior MA or PV occlusion.
Anesthetized male Wistar rats (250-300 g) underwent laparotomy followed by MA or PV occlusion for 40 min. After 120 min of reperfusion, small bowel tissue was collected. The expression of heat shock protein (HSP)-32 and HSP70 was evaluated to compare physiological stress responses between groups. Metabolic profiles were obtained using (1)H-nuclear magnetic resonance spectroscopy (NMR)-based quantitative metabolomics. Histological injury of small bowel was graded from 0 (normal) to 4 (extensive ischemic damage).
Protein expression of HSP32 and HSP70 increased when compared to sham but was not different in the MA I/R and PV I/R groups. Metabolic profiles demonstrated decreased glucose levels and highly elevated tissue lactate and amino acids and fatty acids following I/R, with more pronounced changes with PV occlusion. Lipid peroxidation was equally increased in both groups, while depletion of reduced glutathione (GSH) was more severe with MA occlusion. The epithelial necrosis score was higher with MA (3.5 ± 0.6) than with PV occlusion (2.3 ± 0.8).
Histological injury of the intestine is less pronounced following PV occlusion, most likely due to higher oxygen and substrate availability during I/R by PV occlusion. This conclusion is supported by a more pronounced metabolic synthetic response (increased glycolysis and fatty acid and amino acid accumulation) with PV occlusion, while oxidative stress was higher with MA occlusion. The inflammatory response showed little difference between the groups.
肠缺血可由肠系膜动脉（MA）闭塞和门静脉（PV）闭塞引起。这些情况下的缺血/再灌注（I/R）损伤的程度和机制可能不同。代谢变化在 I/R 早期出现。本研究比较了由于 MA 或 PV 闭塞引起的小肠 I/R 时组织学、炎症和代谢反应的差异。
麻醉雄性 Wistar 大鼠（250-300g）行剖腹术，随后行 MA 或 PV 闭塞 40min。再灌注 120min 后，采集小肠组织。评估热休克蛋白（HSP）-32 和 HSP70 的表达，以比较各组之间的生理应激反应。使用（1）H-核磁共振波谱（NMR）基于定量代谢组学获得代谢谱。小肠组织学损伤评分从 0（正常）到 4（广泛缺血损伤）。
与假手术组相比，HSP32 和 HSP70 的蛋白表达增加，但 MA I/R 和 PV I/R 组之间无差异。代谢谱显示，I/R 后葡萄糖水平降低，组织中乳酸和氨基酸及脂肪酸水平显著升高，PV 闭塞时变化更为明显。两组的脂质过氧化均增加，而 MA 闭塞时还原型谷胱甘肽（GSH）的耗竭更为严重。MA 组（3.5±0.6）的上皮坏死评分高于 PV 组（2.3±0.8）。
与 MA 闭塞相比，PV 闭塞后肠组织损伤程度较轻，这很可能是由于 I/R 时 PV 闭塞提供了更高的氧气和底物。这一结论得到了以下事实的支持：与 MA 闭塞相比，PV 闭塞时代谢合成反应更为明显（糖酵解和脂肪酸及氨基酸积累增加），而 MA 闭塞时氧化应激更高。两组之间的炎症反应差异不大。
