Basic Research
Copyright ©2005 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 28, 2005; 11(44): 6981-6987
Published online Nov 28, 2005. doi: 10.3748/wjg.v11.i44.6981
Exogenous acid fibroblast growth factor inhibits ischemia-reperfusion-induced damage in intestinal epithelium via regulating P53 and P21WAF-1 expression
Wei Chen, Xiao-Bing Fu, Shi-Li Ge, Wen-Juan Li, Tong-Zhu Sun, Zhi-Yong Sheng
Wei Chen, Xiao-Bing Fu, Wen-Juan Li, Tong-Zhu Sun, Zhi-Yong Sheng, Key Research Laboratory of Wound Repair, Burns Institute, 304th Clinical Department, General Hospital of PLA, Beijing 100037, China
Shi-Li Ge, Institute of Radiation Medicine, Beijing 100850, China
Author contributions: All authors contributed equally to the work.
Supported by the National Natural Science Foundation of China, No. 30400172, 30230370, and the National Basic Science and Development programme (973 programme, 2005 CB 522603)
Correspondence to: Professor Xiao-Bing Fu, MD, Key Research Laboratory of Wound Repair, Burns Institute, 304th Clinical Department, General Hospital of PLA, 51 Fu cheng Road, Beijing 100037, China.
Telephone: +86-10-66867396 Fax: +86-10-88416390
Received: November 12, 2004
Revised: February 15, 2005
Accepted: February 18, 2005
Published online: November 28, 2005

AIM: To detect the effect of acid fibroblast growth factor (aFGF) on P53 and P21WAF-1 expression in rat intestine after ischemia-reperfusion (I-R) injury in order to explore the protective mechanisms of aFGF.

METHODS: Male rats were randomly divided into four groups, namely intestinal ischemia-reperfusion group (R), aFGF treatment group (A), intestinal ischemia group (I), and sham-operated control group (C). In group I, the animals were killed after 45 min of superior mesenteric artery (SMA) occlusion. In groups R and A, the rats sustained for 45 min of SMA occlusion and were treated with normal saline (0.15 mL) and aFGF (20 μg/kg, 0.15 mL), then sustained at various times for up to 48 h after reperfusion. In group C, SMA was separated, but without occlusion. Apoptosis in intestinal villi was determined with terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling technique (TUNEL). Intestinal tissue samples were taken not only for RT-PCR to detect P53 and P21WAF-1 gene expression, but also for immunohistochemical analysis to detect P53 and P21WAF-1 protein expression and distribution.

RESULTS: In histopathological study, ameliorated intestinal structures were observed at 2, 6, and 12 h after reperfusion in A group compared to R group. 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 A group, which were apparently lower than those in R group at their matched time points (50.67±6.95)%, (54.17±7.86)%, and (64.33±6.47)%, respectively, (P<0.05)). The protein contents of P53 and P21WAF-1 were both significantly decreased in A group compared to R group (P<0.05) at 2-12 h after reperfusion, while the mRNA levels of P53 and P21WAF-1 in A group were obviously lower than those in R group at 6-12 h after reperfusion (P<0.05).

CONCLUSION: P53 and P21WAF-1 protein accumulations are associated with intestinal barrier injury induced by I-R insult, while intravenous aFGF can alleviate apoptosis of rat intestinal cells by inhibiting P53 and P21WAF-1 protein expression.

Keywords: Acid fibroblast growth factor, Ischemia, Reperfusion, P53 gene, P21WAF-1 gene