Intravenous acid fibroblast growth factor protects intestinal mucosal cells against ischemia-reperfusion injury via regulating Bcl-2/Bax expression.
OBJECTIVE
To detect the effect of acid fibroblast growth factor (aFGF) on apoptosis and gene expression of bax and bcl-2 gene in rat intestine after ischemia/reperfusion (I/R) injury, and to explore the protective mechanisms of aFGF.


METHODS
One hundred and eight Wistar rats were randomly divided into sham-operated control group (C) (n = 6), intestinal ischemia group (I) (n = 6), aFGF treatment group (A) (n = 48) and intestinal ischemia-reperfusion group (R) (n = 48). In group I, the animals were killed after 45 min of superior mesenteric artery (SMA) occlusion, while in groups R and A, the rats sustained 45 min of SMA occlusion and were then treated with normal saline and aFGF, respectively, sustained 15 min, 30 min, 1, 2, 6, 12, 24, or 48 h of reperfusion, respectively. In group C, SMA was separated, but without occlusion. Apoptosis in intestinal villus was determined with terminal deoxynucleotidyl transferase mediated dUTP-biotin nick-end labeling technique (TUNEL). Intestinal tissue samples were taken not only for detection of bax and bcl-2 gene expression by RT-PCR, but also for detection of bax and bcl-2 protein expression and distribution by immunohistochemical analysis.


RESULTS
The rat survival rates in aFGF treated group were higher than group R (P<0.05) and the improvement of intestinal histological structures was observed at 2, 6, and 12 h after the reperfusion in group A compared with group R. The apoptotic rates were (41.17+/-3.49)%, (42.83+/-5.23)% and (53.33+/-6.92)% at 2, 6 and 12 h after reperfusion, respectively in group A, apparently less than those of group R at matched time points (50.67+/-6.95, 54.17+/-7.86, 64.33+/-6.47, respectively) (P<0.05). The bax gene transcription and translation were significantly decreased in group A vs group R, while mRNA and protein contents of Bcl-2 in group A were obviously higher than those in group R during 2-12 h period after reperfusion.


CONCLUSIONS
The changes in histological structure and the increment of apoptotic rate indicated that the intestinal barrier was damaged after intestinal I/R injury, whilst intravenous aFGF could alleviate apoptosis induced by ischemia and reperfusion in rat intestinal tissues, in which genes of bax and bcl-2 might play important roles.
Chen
Wei
W
Wound Healing and Cell Biology Laboratory, 304th Hospital, Burns Institute, Trauma Center of Postgraduate Medical College, 51 Fu Cheng Road, Beijing 100037, China.
Fu
Xiao-Bing
XB
Ge
Shi-Li
SL
Sun
Tong-Zhu
TZ
Zhou
Gang
G
Han
Bing
B
Du
Yi-Ri
YR
Li
Hai-Hong
HH
Sheng
Zhi-Yong
ZY
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D007275:Injections, Intravenous; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000473:pathology; D008297:Male; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D051028:bcl-2-Associated X Protein
C494828:Bax protein, rat; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D016220:Fibroblast Growth Factor 1