Increased gut permeability after hemorrhage is associated with upregulation of local and systemic IL-6
Increased gut permeability after hemorrhage is associated with upregulation of local and systemic IL-6
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DOI：
10.1006/jsre.1998.5385
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发表时间：
1998-09-01
影响因子：
2.2
通讯作者：
Chaudry, IH
中科院分区：
文献类型：
--
作者：
Wang, WY;Smail, N;Chaudry, IH
虽然出血后肠屏障功能衰竭是一个有据可查的事件，但其潜在机制仍知之甚少。因此，本研究的目的是确定出血后肠通透性的改变是否与局部和全身白细胞介素-6（IL-6）的上调有关。为了研究这一点，对大鼠进行剖腹手术（即，创伤诱导），流血的至40 mm Hg的平均动脉压并维持在40 mm Hg的平均动脉压，直到40%的流出血量以林格氏乳酸盐的形式返回。然后用四倍体积的具有林格氏乳酸盐的流出血液复苏动物60分钟。在复苏后1.5小时，形成远端小肠的体内结扎环，并通过荧光光谱法分析4-kDa荧光素异硫氰酸酯缀合的葡聚糖（FD 4）从肠腔进入门静脉和颈动脉血液的通道，从门静脉和颈动脉收集样品并测定血浆IL-B。从远端小肠上皮内淋巴细胞分离和体外培养24小时，有或没有抗大鼠CD 3单克隆抗体刺激。测定新鲜分离的细胞中的IL-6活性及其由培养的淋巴细胞释放。在另一组平行实验中，用放射性微球测定肠灌注和门静脉血流量。结果表明，FD 4通过小肠壁的腔-血通道在出血和复苏后1.5 h显著增加，并且与肠灌注和门静脉血流量减少相关。出血复苏后1.5h，门静脉和颈动脉血浆IL-6水平明显升高。此外，血浆IL-6和FD 4浓度之间观察到显著相关性。在新鲜分离的细胞中，老年大鼠的IL-6活性较高。增加IL-6释放培养的淋巴细胞也观察到无论有或没有抗大鼠CD 3单克隆抗体刺激。因此，创伤-出血和复苏后肠通透性增加似乎与全身和肠IL-6上调有关。(C)北京：科学出版社.
Although intestinal barrier failure after hemorrhage is a well-documented event, the underlying mechanism is poorly understood. The aim of this study, therefore, was to determine whether altered intestinal permeability after hemorrhage is associated with upregulation of local and systemic interleukin-6 (IL-6). To study this, rats underwent laparotomy (i,e,, trauma induced) and were bled to and maintained at a mean arterial pressure of 40 mm Hg until 40% of the shed blood volume was returned in the form of Ringer's lactate. The animals were then resuscitated with four times the volume of shed blood with Ringer's lactate over 60 min. At 1.5 h postresuscitation, an in vivo ligated loop of a distal small intestine was formed and the passage of 4-kDa fluorescein isothiocyanate-conjugated dextran (FD4) from the intestinal lumen into the portal vein and carotid artery blood was analyzed by fluorescence spectrometry, Samples from the portal vein and a carotid artery were collected and plasma IL-B was assayed. Intraepithelial lymphocytes from a distal small intestine were isolated and cultured in vitro for 24 h with or without anti-rat CD3 monoclonal antibody stimulation. IL-6 activity in freshly isolated cells and its release by cultured lymphocytes were determined. Intestinal perfusion and portal blood flow were determined by radioactive microspheres in another set of parallel experiments. The results indicate that lumen-to-blood passage of FD4 through the wall of the small intestine increased significantly at 1.5 h after hemorrhage and resuscitation and was associated with decreased intestinal perfusion and portal blood flow. Plasma IL-6 levels in the portal vein and carotid artery markedly increased at 1.5 h after hemorrhage and resuscitation. In addition, a significant correlation was observed between plasma IL-6 and FD4 concentrations. Higher IL-6 activity in freshly isolated cells was found in hemorrhaged rats. Increased IL-6 release by cultured lymphocytes was also observed either with or without anti-rat CD3 monoclonal antibody stimulation. Thus, the increased intestinal permeability following trauma-hemorrhage and resuscitation appears to be associated with systemic and intestinal IL-6 upregulation. (C) 1998 Academic Press.