Aosa Taishi, Chiba Seiichi, Kitamura Hirokazu, Ina Keisuke, Tatsukawa Shuji, Moriwaki Chinatsu, Wei Huixing, Gotoh Koro, Masaki Takayuki, Kakuma Tetsuya, Shibata Hirotaka, Fujikura Yoshihisa
Department of Molecular Anatomy, Faculty of Medicine, Oita University, Hasama-machi, Yufu, Oita, Japan.
Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Oita University, Hasama-machi, Yufu, Oita, Japan.
Histol Histopathol. 2016 Jul;31(7):807-17. doi: 10.14670/HH-11-716. Epub 2016 Jan 5.
Stress-induced inflammatory responses in the portal system are characterized by elevations in serum concentrations of interleukin-6 (IL-6) and endotoxins such as lipopolysaccharides (LPS). LPS translocation from the intestinal to the capillary lumen occurs via LPS endocytosis by the capillary endothelium. Because the capillary endothelium of the small intestinal submucosa is fenestrated, we determined the role of pore modifications within the fenestrated endothelium in relaying inflammatory stress responses in the portal vein. We evaluated changes in the diameter and density of endothelial pores of the lamina propria of intestinal villi induced by continuous light (CL) exposure for 48 h and the correlation between these changes and serum IL-6 concentration in the portal vein in a rat model. We found significant increases in both the pore diameter and density, accompanied by a significant increase in portal IL-6 concentration; these changes were significantly attenuated by pretreatment with propranolol, a beta adrenergic receptor antagonist. In contrast, intravenous noradrenaline administration mimicked CL-induced modifications of the diameter and density of pores and the elevation of portal vein IL-6 concentration. These findings suggested that stress-induced inflammatory responses in the portal system may be a part of the modifications of the endothelial pores triggered by sympathetic activation.
门静脉系统中应激诱导的炎症反应的特征是血清白细胞介素-6（IL-6）浓度升高以及脂多糖（LPS）等内毒素水平升高。LPS从肠道转移至毛细血管腔是通过毛细血管内皮细胞的LPS内吞作用实现的。由于小肠黏膜下层的毛细血管内皮有窗孔，我们确定了有窗孔内皮细胞内孔道改变在传递门静脉炎症应激反应中的作用。我们评估了在大鼠模型中，连续光照（CL）暴露48小时诱导的肠绒毛固有层内皮孔道直径和密度的变化，以及这些变化与门静脉血清IL-6浓度之间的相关性。我们发现孔道直径和密度均显著增加，同时门静脉IL-6浓度也显著升高；用β肾上腺素能受体拮抗剂普萘洛尔预处理可显著减轻这些变化。相反，静脉注射去甲肾上腺素模拟了CL诱导的孔道直径和密度改变以及门静脉IL-6浓度升高。这些发现表明，门静脉系统中应激诱导的炎症反应可能是交感神经激活引发的内皮孔道改变的一部分。
