Yang Runkuan, Han Xiaonan, Uchiyama Takashi, Watkins Simon K, Yaguchi Arino, Delude Russell L, Fink Mitchell P
Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA.
Am J Physiol Gastrointest Liver Physiol. 2003 Sep;285(3):G621-9. doi: 10.1152/ajpgi.00177.2003. Epub 2003 May 28.
We sought to determine the role of IL-6 as a mediator of the alterations in gut barrier function that occur after hemorrhagic shock and resuscitation (HS/R). C57Bl/6 wild-type (WT) and IL-6 knockout (KO) mice on a C57Bl/6 background were subjected to either a sham procedure or HS/R. Organ and tissue samples were obtained 4 h after resuscitation. In WT mice, HS/R significantly increased ileal mucosal permeability to fluorescein isothiocyanate-labeled dextran (average molecular mass, 4 kDa) and bacterial translocation to mesenteric lymph nodes. These alterations in gut barrier function were not observed in IL-6 KO animals. HS/R increased ileal steady-state mRNA levels for IL-6, TNF, and IL-10 in WT but not in IL-6 KO mice. Ileal mucosal expression of the tight junction protein, ZO-1, decreased after HS/R in WT but not IL-6 KO mice. Collectively, these data support the view that expression of IL-6 is essential for the development of gut barrier dysfunction after HS/R.
我们试图确定白细胞介素-6（IL-6）作为失血性休克和复苏（HS/R）后肠道屏障功能改变的介质所起的作用。将C57Bl/6背景的C57Bl/6野生型（WT）和IL-6基因敲除（KO）小鼠进行假手术或HS/R处理。复苏4小时后获取器官和组织样本。在野生型小鼠中，HS/R显著增加了回肠黏膜对异硫氰酸荧光素标记葡聚糖（平均分子量4 kDa）的通透性以及细菌向肠系膜淋巴结的移位。在IL-6基因敲除动物中未观察到肠道屏障功能的这些改变。HS/R增加了野生型小鼠而非IL-6基因敲除小鼠回肠中IL-6、肿瘤坏死因子（TNF）和白细胞介素-10（IL-10）的稳态mRNA水平。紧密连接蛋白ZO-1在野生型小鼠HS/R后回肠黏膜的表达降低，但在IL-6基因敲除小鼠中未降低。总体而言，这些数据支持以下观点：IL-6的表达对于HS/R后肠道屏障功能障碍的发生至关重要。
