Attenuated portal hypertension in germ‐free mice: Function of bacterial flora on the development of mesenteric lymphatic and blood vessels

作者：Sheida Moghadamrad, Kathy D. McCoy, Markus B. Geuking, Hans Sägesser, Jorum Kirundi, Andrew J. Macpherson, Andrea De Gottardi · 发表于：Hepatology · 年份：2015 · DOI：10.1002/hep.27698 · 被引用次数：59 · 研究领域：Liver Disease and Transplantation、Pancreatitis Pathology and Treatment、Abdominal vascular conditions and treatments

UNLABELLED: Intestinal bacterial flora may induce splanchnic hemodynamic and histological alterations that are associated with portal hypertension (PH). We hypothesized that experimental PH would be attenuated in the complete absence of intestinal bacteria. We induced prehepatic PH by partial portal vein ligation (PPVL) in germ-free (GF) or mice colonized with altered Schaedler's flora (ASF). After 2 or 7 days, we performed hemodynamic measurements, including portal pressure (PP) and portosystemic shunts (PSS), and collected tissues for histomorphology, microbiology, and gene expression studies. Mice colonized with intestinal microbiota presented significantly higher PP levels after PPVL, compared to GF, mice. Presence of bacterial flora was also associated with significantly increased PSS and spleen weight. However, there were no hemodynamic differences between sham-operated mice in the presence or absence of intestinal flora. Bacterial translocation to the spleen was demonstrated 2 days, but not 7 days, after PPVL. Intestinal lymphatic and blood vessels were more abundant in colonized and in portal hypertensive mice, as compared to GF and sham-operated mice. Expression of the intestinal antimicrobial peptide, angiogenin-4, was suppressed in GF mice, but increased significantly after PPVL, whereas other angiogenic factors remained unchanged. Moreover, colonization of GF mice with ASF 2 days after PPVL led to a significant increase in intestinal blood vessels, compared to con...