title: Non-mitogenic acidic fibroblast growth factor reduces intestinal dysfunction induced by ischemia and reperfusion injury in rats.
abstract: BACKGROUND
  Acidic fibroblast growth factor (aFGF) has potentially therapeutic uses in some diseases, but the mitogenic activity of aFGF has been found to contribute to several human pathologies, so the extensive applications of wild-type aFGF have been limited. The purpose of the present study was to explore the effects and mechanisms of wild-type (aFGF) and non-mitogenic aFGF on gut ischemia-reperfusion injury in rats.
  
  
  METHODS
  Rat intestinal ischemia-reperfusion injury (I/R) was produced by clamping the superior mesenteric artery (SMA) for 45 min followed by reperfusion. One hundred and fourteen rats were randomly divided into four groups: sham operation (group C, n = 6), intestinal I/R + 0.1 mL saline (group S, n = 36), intestinal I/R + 4 microg/0.1 mL wild-type aFGF (group W, n = 36) and intestinal I/R + 4 microg/0.1 mL modified aFGF (i.e. non-mitogenic aFGF; group M, n = 36). According to different periods after reperfusion, groups S, W and M were further divided into 0.5-, 1-, 2-, 6-, 12- and 24-h subgroups. The contents of D-lactate and nitrite/nitrate were determined, the changes of intestinal histology were analyzed, the protein expressions of caspase-3, extracellular signal-regulated kinase (ERK)1/2, and p38 were detected by western blot, and apoptotic cells were examined by the terminal deoxynucleotidyl transferase (TdT)-mediated dUDP-biotin nick end labeling (TUNEL) assay at 0.5, 1, 2, 6, 12 and 24 h after I/R, respectively.
  
  
  RESULTS
  Compared with rats in group S, intestinal histological damage, apoptotic index, d-lactate content and nitrite/nitrate level all decreased significantly in group W and group M rats. However, there was no difference between rats treated with wild-type aFGF and those with non-mitogenic aFGF. The protein expression of caspase-3, ERK1/2, and p38 in saline-treated rats was higher than those in aFGF-treated rats.
  
  
  CONCLUSIONS
  Both types of aFGF had protective effects on gut I/R and there was no significant difference between the two aFGF. The protective effects of aFGF may come from the non-mitogenic activity rather than the mitogenic activity of aFGF in tissue repair, indicating a potentially clinical use for the non-mitogenic effects of aFGF in preventing visceral organ injury triggered by I/R injury in the future.
authors.affiliation: Wound Healing and Cell Biology Laboratory, Burns Institute, First Affiliated Hospital, General Hospital of PLA, Trauma Center of Postgraduate Medical College, Beijing, China.
authors.forename: Hai-Hong
authors.initials: HH
authors.lastname: Li
authors.forename: Xiao-Bing
authors.initials: XB
authors.lastname: Fu
authors.forename: Tong-Zhu
authors.initials: TZ
authors.lastname: Sun
authors.forename: Cun-Liang
authors.initials: CL
authors.lastname: Cai
authors.forename: Gang
authors.initials: G
authors.lastname: Zhou
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Sheng
mesh_terms: D000818:Animals; D016220:Fibroblast Growth Factor 1 / Q000627:therapeutic use*; D007422:Intestines / Q000098:blood supply* / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy*
chemical_list: D016220:Fibroblast Growth Factor 1