Juel Ingebjørg S, Solligård Erik, Tvedt Kåre E, Skogvoll Eirik, Jynge Per, Beisvag Vidar, Erlandsen Sten Even, Sandvik Arne K, Aadahl Petter, Grønbech Jon Erik
Department of Surgery, St. Olav University Hospital, NO-7006 Trondheim, Norway.
Scand J Clin Lab Invest. 2008;68(2):106-16. doi: 10.1080/00365510701534833. Epub 2007 Nov 21.
Ischaemic preconditioning may protect the intestine from subsequent prolonged ischaemia. This study evaluates whether a much longer initial ischaemia, encountered clinically, may modify intestinal resistance to further ischaemia in a pig model.
After cross-clamping of the superior mesenteric artery for 1 h, the intestine was either reperfused for 8 h or a second cross-clamping for 1 h was performed at 4 h of reperfusion. Based on microarray analysis of intestinal samples at 1, 4 and 8 h of reperfusion, mRNA of selected genes was measured with QRT-PCR.
The first ischaemic period caused exfoliation of surface epithelial cells from the basement membrane comprising about 90 % of the villi tips, a marked increase in permeability and depletion of ATP. The second ischaemic challenge caused about 30 % less denudation of the basement membrane (p = 0.008), no increase in permeability (p = 0.008) and less depletion of ATP (p = 0.039). mRNAs for superoxide dismutase 2, heat shock proteins and signal transducer and activator of transcription 3, which may protect against ischaemia/reperfusion injury, were up-regulated throughout the reperfusion period. mRNAs for matrix metalloproteinase 1, connexin 43 and peripheral myelin 22, which may be associated with cell migration or tight junctions, showed a particular up-regulation at 4 h of reperfusion.
One hour of initial ischaemia followed by 4 h of reperfusion is associated with increased intestinal resistance to further ischaemia. The differential regulation of genes identified in this study provides working hypotheses for mechanisms behind this observation.
缺血预处理可能保护肠道免受随后的长时间缺血影响。本研究评估临床上遇到的长得多的初始缺血是否会改变猪模型中肠道对进一步缺血的耐受性。
在肠系膜上动脉交叉夹闭1小时后，肠道要么再灌注8小时，要么在再灌注4小时时进行第二次交叉夹闭1小时。基于再灌注1、4和8小时时肠道样本的微阵列分析，用实时定量聚合酶链反应（QRT-PCR）测量所选基因的信使核糖核酸（mRNA）。
第一个缺血期导致表面上皮细胞从基底膜脱落，约占绒毛顶端的90%，通透性显著增加，三磷酸腺苷（ATP）耗竭。第二次缺血刺激导致基底膜剥脱减少约30%（p = 0.008），通透性无增加（p = 0.008），ATP耗竭减少（p = 0.039）。超氧化物歧化酶2、热休克蛋白以及信号转导和转录激活因子3的mRNA，它们可能对缺血/再灌注损伤具有保护作用，在整个再灌注期均上调。基质金属蛋白酶1、连接蛋白43和外周髓磷脂22的mRNA，它们可能与细胞迁移或紧密连接有关，在再灌注4小时时出现特别上调。
初始缺血1小时后再灌注4小时与肠道对进一步缺血的耐受性增加有关。本研究中鉴定出的基因差异调节为这一观察结果背后的机制提供了可行的假设。
