title: High altitude increases the expression of hypoxia-inducible factor 1α and inducible nitric oxide synthase with intest-inal mucosal barrier failure in rats.
abstract: BACKGROUND
  The failure of intestinal mucosal barrier may induce multiple organ dysfunction and systemic inflammatory response syndrome, but little work has been done on whether hypobaric hypoxia related to the failure of intestinal mucosal barrier.
  
  
  OBJECTIVE
  To study the expression of hypoxia-inducible factor 1α (HIF-1α), inducible nitric oxide synthase (iNOS) and morphological changes of intestinal mucosa in albino rats at different altitude.
  
  
  METHODS
  30 male Wistar rats raised in plain for one month were randomly divided into 3 groups: Plain 500 m group (n=10), High-altitude (HA) 3842 m group (n=10) and HA4767 m group (n=10). Each group was delivered to different altitude area at the same shipping time and executed after 3 days' exposure to different altitude. Intestinal segments with the same location of all rats were removed for morphological analyses. Morphologic parameters (villous height, crypt depth, mucosal wall thickness and villous surface area) were measured by optical and scanning electron microscope. The expression of iNOS and HIF-1α were detected by immunohistochemistry.
  
  
  RESULTS
  Morphological indexes in higher altitude groups were exacerbated obviously compared with those of lower altitude groups. While the expression of iNOS and HIF-1α in higher altitude groups were significantly increased than those of lower altitude groups. Linear correlation analysis showed that the expression of iNOS was positively correlated with that of HIF-1α.
  
  
  CONCLUSIONS
  Hypobaric hypoxia increases the expression of HIF-1α and iNOS in intestinal mucosa, however exacerbates the mucous morphologic parameters with altitude increasing. HIF-1α may regulate the expression of iNOS and be involved in the damage of intestinal mucosa.
authors.affiliation: Department of Gastroenterology, Lanzhou General Hospital of Lanzhou Military Command Lanzhou 730050, China.
authors.forename: Fangxin
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Lanzhou General Hospital of Lanzhou Military Command Lanzhou 730050, China.
authors.forename: Wenming
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Clinical Laboratory, Lanzhou General Hospital of Lanzhou Military Command Lanzhou 730050, China.
authors.forename: Zhiyun
authors.initials: Z
authors.lastname: Deng
authors.affiliation: Department of Gastroenterology, Lanzhou General Hospital of Lanzhou Military Command Lanzhou 730050, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Gastroenterology, Lanzhou General Hospital of Lanzhou Military Command Lanzhou 730050, China.
authors.forename: Jiucong
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Lanzhou General Hospital of Lanzhou Military Command Lanzhou 730050, China.
authors.forename: Shangxin
authors.initials: S
authors.lastname: Deng
authors.affiliation: Department of Gastroenterology, Lanzhou General Hospital of Lanzhou Military Command Lanzhou 730050, China.
authors.forename: Jiayu
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, Lanzhou General Hospital of Lanzhou Military Command Lanzhou 730050, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Ma
authors.affiliation: Department of Gastroenterology, Lanzhou General Hospital of Lanzhou Military Command Lanzhou 730050, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Lanzhou General Hospital of Lanzhou Military Command Lanzhou 730050, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Gastroenterology, Lanzhou General Hospital of Lanzhou Military Command Lanzhou 730050, China.
authors.forename: Shengchao
authors.initials: S
authors.lastname: Kang
authors.affiliation: Department of Gastroenterology, Lanzhou General Hospital of Lanzhou Military Command Lanzhou 730050, China.
authors.forename: Xiufeng
authors.initials: X
authors.lastname: Wang
mesh_terms: D000531:Altitude; D000532:Altitude Sickness / Q000201:enzymology* / Q000473:pathology; D000818:Animals; D004195:Disease Models, Animal; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007082:Ileum / Q000201:enzymology* / Q000648:ultrastructure; D007413:Intestinal Mucosa / Q000201:enzymology* / Q000648:ultrastructure; D016014:Linear Models; D008297:Male; D008855:Microscopy, Electron, Scanning; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D010539:Permeability; D017208:Rats, Wistar; D013997:Time Factors; D015854:Up-Regulation
chemical_list: C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat
keywords: High-altitude; hypoxia; hypoxia inducible factor-1α; inducible nitric oxide synthase; intestinal mucosal barrier