Viñuales Carmen, Gascón Sonia, Barranquero Cristina, Osada Jesús, Rodríguez-Yoldi Ma Jesús
Unidad de Fisiología, Departamento de Farmacología y Fisiología, Facultad de Veterinaria, Universidad de Zaragoza, Zaragoza, Spain.
Cell Physiol Biochem. 2012;30(1):173-86. doi: 10.1159/000339056. Epub 2012 Jun 15.
BACKGROUND/AIMS: Recent studies from our laboratory have shown that nitric oxide is involved in the IL-1β-induced inhibition of D-fructose intestinal transport in rabbits. The aim of this work was to further the studies of IL-1β effect on D-galactose absorption in a septic state induced by intravenous administration of this cytokine.
Galactose intestinal absorption was assessed employing three techniques: sugar uptake in jejunum everted rings, transepithelial flux in Ussing-type chambers and uptake assays in brush border membrane vesicles. The level of the Na(+)/D-glucose cotransporter (SGLT1) expression was analyzed by Western blot.
In sepsis condition the body temperature was increased and studies on cellular intestinal integrity have not shown modifications in the brush border membrane. However, D-galactose absorption across mucosa of jejunum was diminished in IL-1β treated rabbits. The levels of SGLT-1 were no significantly different in both animal groups (control and IL-1β treated), indicating that the cytokine could induce a reduction in the SGLT-1 functionality. The inhibition was significantly reversed by the activation of several PKC, PKA, MAPKs and nuclear factor (NF)-ĸB inhibitors administered 15 min before the IL-1β.
The inhibitory effect of IL-1β on D-galactose absorption across mucosal side of enterocyte could be mediated by the activation of several kinases and nuclear factor (NF)-ĸB.
背景/目的:我们实验室最近的研究表明,一氧化氮参与白细胞介素-1β(IL-1β)诱导的家兔D-果糖肠道转运抑制。本研究旨在进一步探讨IL-1β对静脉注射该细胞因子诱导的脓毒症状态下D-半乳糖吸收的影响。
采用三种技术评估半乳糖的肠道吸收:空肠外翻环中的糖摄取、Ussing型小室中的跨上皮通量以及刷状缘膜囊泡中的摄取测定。通过蛋白质印迹法分析钠/ D-葡萄糖共转运蛋白(SGLT1)的表达水平。
在脓毒症状态下,体温升高,对肠道细胞完整性的研究未显示刷状缘膜有改变。然而,IL-1β处理的家兔空肠黏膜对D-半乳糖的吸收减少。两组动物(对照组和IL-1β处理组)的SGLT-1水平无显著差异,表明该细胞因子可导致SGLT-1功能降低。在IL-1β注射前15分钟给予几种蛋白激酶C(PKC)、蛋白激酶A(PKA)、丝裂原活化蛋白激酶(MAPK)和核因子(NF)-κB抑制剂激活后,抑制作用显著逆转。
IL-1β对肠上皮细胞黏膜侧D-半乳糖吸收的抑制作用可能是由几种激酶和核因子(NF)-κB的激活介导的。