deZoeten Edwin F, Battista Kayla D, Colson Steven B, Lovell Mark A, Kessler Brittelle E, Isfort Robert W, Fennimore Blair P, Onyiah Joseph C, Kao Daniel J, Yeckes Alyson, Keely Simon, Murray Monica, Hoffenberg Edward J, Colgan Sean P, Gerich Mark E
Department of Pediatrics and the Digestive Health Institute, University of Colorado School of Medicine/Children's Hospital Colorado, Aurora, CO, USA.
Department of Medicine and Mucosal Inflammation Program, Division of Gastroenterology and Hepatology, University of Colorado School of Medicine, Aurora, CO, USA.
Hypoxia (Auckl). 2020 Feb 10;8:1-12. doi: 10.2147/HP.S219049. eCollection 2020.
Inflammation results in significant shifts in tissue metabolism. Recent studies indicate that inflammation and hypoxia occur concomitantly. We examined whether circulating and tissue markers of hypoxia could serve as surrogate indicators of disease severity in adult and pediatric patients with inflammatory bowel disease (IBD).
Serum and colonic biopsies were obtained from pediatric subjects with active IBD colitis and adult subjects with active and inactive ulcerative colitis, along with healthy non-colitis controls of all ages. Disease activity was evaluated by endoscopy and histopathology. Levels of serum hypoxia markers (macrophage inflammatory protein-3α [MIP-3α], vascular endothelial growth factor [VEGF], and erythropoietin [EPO]) were measured.
Children with active IBD colitis had higher levels of serum MIP-3α and VEGF compared to non-colitis controls (p<0.01 and p<0.05, respectively). In adult subjects with endoscopically active ulcerative colitis, serum MIP-3α and EPO were significantly elevated compared to non-colitis controls (both p<0.01). In parallel, analysis of colon tissue MIP-3α mRNA and protein in pediatric subjects revealed increased expression in those with IBD colitis compared to controls (p<0.05 and p<0.01 for mRNA and protein, respectively). Serum MIP-3α and VEGF significantly increased with histology grade.
Peripheral blood hypoxia markers may be useful indicators of disease activity for pediatric and adult IBD patients.
炎症会导致组织代谢发生显著变化。最近的研究表明，炎症和缺氧同时发生。我们研究了缺氧的循环和组织标志物是否可作为成人和儿童炎症性肠病（IBD）患者疾病严重程度的替代指标。
从患有活动性IBD结肠炎的儿科受试者、患有活动性和非活动性溃疡性结肠炎的成人受试者以及所有年龄段的健康非结肠炎对照者中获取血清和结肠活检样本。通过内镜检查和组织病理学评估疾病活动度。测量血清缺氧标志物（巨噬细胞炎性蛋白-3α [MIP-3α]、血管内皮生长因子 [VEGF] 和促红细胞生成素 [EPO]）的水平。
与非结肠炎对照者相比，患有活动性IBD结肠炎的儿童血清MIP-3α和VEGF水平更高（分别为p<0.01和p<0.05）。在内镜检查为活动性溃疡性结肠炎的成人受试者中，血清MIP-3α和EPO与非结肠炎对照者相比显著升高（均为p<0.01）。同时，对儿科受试者结肠组织MIP-3α mRNA和蛋白的分析显示，与对照者相比，IBD结肠炎患者的表达增加（mRNA和蛋白分别为p<0.05和p<0.01）。血清MIP-3α和VEGF随组织学分级显著增加。
外周血缺氧标志物可能是儿科和成人IBD患者疾病活动度的有用指标。
