Fibrinogen deficiency suppresses the development of early and delayed radiation enteropathy
Fibrinogen deficiency suppresses the development of early and delayed radiation enteropathy作者机构：Division of Radiation Health University of Arkansas for Medical Sciences
出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)
年 卷 期：2017年第23卷第26期
页 面：4701-4711页
核心收录：
学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学]
基 金：Supported by Arkansas Space Grant Consortium and National Space Biomedical Research Institute through National Aeronautics and Space Administration,No.NNX15AK32A(RP)and No.RE03701(MH-J) National Institutes of Health,No.P20 GM109005(MH-J)
主 题：Radiation enteropathy Knockout mouse model Fibrinogen Inflammation Fibrosis Ionizing radiation
摘 要：To determine the mechanistic role of fibrinogen, a key regulator of inflammation and fibrosis, in early and delayed radiation enteropathy. METHODSFibrinogen wild-type (Fib+/+), fibrinogen heterozygous (Fib+/-), and fibrinogen knockout (Fib-/-) mice were exposed to localized intestinal irradiation and assessed for early and delayed structural changes in the intestinal tissue. A 5-cm segment of ileum of mice was exteriorized and exposed to 18.5 Gy of x-irradiation. Intestinal tissue injury was assessed by quantitative histology, morphometry, and immunohistochemistry at 2 wk and 26 wk after radiation. Plasma fibrinogen level was measured by enzyme-linked immunosorbent assay. RESULTSThere was no difference between sham-irradiated Fib+/+ and Fib+/- mice in terms of fibrinogen concentration in plasma and intestinal tissue, intestinal histology, morphometry, intestinal smooth muscle cell proliferation, and neutrophil infiltration. Therefore, Fib+/- mice were used as littermate controls. Unlike sham-irradiated Fib+/+ and Fib+/- mice, no fibrinogen was detected in the plasma and intestinal tissue of sham-irradiated Fib-/- mice. Moreover, fibrinogen level was not elevated after irradiation in the intestinal tissue of Fib-/- mice, while significant increase in intestinal fibrinogen level was noticed in irradiated Fib+/+ and Fib+/- mice. Importantly, irradiated Fib-/- mice exhibited substantially less overall intestinal structural injury (RIS, P = 0.000002), intestinal wall thickness (P = 0.003), intestinal serosal thickness (P = 0.009), collagen deposition (P = 0.01), TGF-β immunoreactivity (P = 0.03), intestinal smooth muscle proliferation (P = 0.046), neutrophil infiltration (P = 0.01), and intestinal mucosal injury (P = 0.0003), compared to irradiated Fib+/+ and Fib+/- mice at both 2 wk and 26 wk. CONCLUSIONThes
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