Jang Hyosun, Lee Janet, Park Sunhoo, Kim Joong Sun, Shim Sehwan, Lee Seung Bum, Han Sung-Honn, Myung Hyunwook, Kim Hyewon, Jang Won-Suk, Lee Sun-Joo, Myung Jae Kyung
Laboratory of Radiation Exposure & Therapeutics, National Radiation Emergency Medical Center, Korea Institute of Radiological and Medical Sciences, Seoul, South Korea.
Department of Pathology, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, South Korea.
Front Pharmacol. 2019 Aug 16;10:892. doi: 10.3389/fphar.2019.00892. eCollection 2019.
Radiation-induced intestinal injury occurred in application of radiotherapy for abdominal and pelvic cancers or in nuclear accidents. Radiation-induced enteritis may be considered an ideal model of gastrointestinal inflammation. The endothelium is a crucial component of inflammation, and the endothelial dysfunction following radiation exposure induces the intestinal proinflammatory response and progression of radiation enteritis. Baicalein (5,6,7-trihydroxyflavonoid) is a flavonoid from used in oriental herbal medicine. Baicalein has been found to have multiple beneficial properties including antioxidant, anti-inflammatory, anti-allergic, and anti-cancer activities. Here, we investigated the therapeutic effects of baicalein on endothelial dysfunction in radiation-induced intestinal inflammation. We performed histological analysis, bacterial translocation, and intestinal permeability assays and also assessed infiltration of leukocytes and inflammatory cytokine expression using a mouse model of radiation-induced enteritis. In addition, to investigate the effect of baicalein in endothelial dysfunction, we analyzed endothelial-derived adherent molecules in human umbilical vein endothelial cells (HUVECs) and irradiated intestinal tissue. Histological damage such as shortening of villi length and impaired intestinal crypt function was observed in the radiation-induced enteritis mouse model. Intestinal damage was attenuated in baicalein-treated groups with improvement of intestinal barrier function. Baicalein inhibited the expression of radiation-induced adherent molecules in HUVECs and intestine of irradiated mouse and decreased leukocyte infiltration in the radiation-induced enteritis. Baicalein could accelerate crypt regeneration recovery of endothelial damage. Therefore, baicalein has a therapeutic effect on radiation-induced intestinal inflammation by attenuating endothelial damage.
腹部和盆腔癌症放疗或核事故中会发生辐射诱导的肠道损伤。辐射性肠炎可被视为胃肠道炎症的理想模型。内皮是炎症的关键组成部分,辐射暴露后的内皮功能障碍会诱发肠道促炎反应和放射性肠炎的进展。黄芩素(5,6,7 - 三羟基黄酮)是一种来自东方草药的黄酮类化合物。已发现黄芩素具有多种有益特性,包括抗氧化、抗炎、抗过敏和抗癌活性。在此,我们研究了黄芩素对辐射诱导的肠道炎症中内皮功能障碍的治疗作用。我们使用辐射诱导肠炎的小鼠模型进行了组织学分析、细菌移位和肠道通透性测定,并评估了白细胞浸润和炎性细胞因子表达。此外,为了研究黄芩素在内皮功能障碍中的作用,我们分析了人脐静脉内皮细胞(HUVECs)和受辐照肠道组织中内皮来源的黏附分子。在辐射诱导肠炎小鼠模型中观察到了如绒毛长度缩短和肠隐窝功能受损等组织学损伤。黄芩素治疗组的肠道损伤减轻,肠道屏障功能得到改善。黄芩素抑制了辐射诱导的HUVECs和受辐照小鼠肠道中黏附分子的表达,并减少了辐射诱导肠炎中的白细胞浸润。黄芩素可加速隐窝再生及内皮损伤的恢复。因此,黄芩素通过减轻内皮损伤对辐射诱导的肠道炎症具有治疗作用。