Exogenous acid fibroblast growth factor inhibits ischemia-reperfusion-induced damage in intestinal epithelium via regulating P53 and P21WAF-1 expression  

作　　者：Wei Chen Xiao-Bing Fu Shi-Li Ge Tong-Zhu Sun Zhi-Yong Sheng 

机构地区：[1]Key Research Laboratory of Wound Repair, Burns Institute, 304^th Clinical Department, General Hospital of PLA,Beijing 100037, China [2]Institute of Radiation Medicine, Beijing 100850, China

出　　处：《World Journal of Gastroenterology》2005年第44期6981-6987,共7页世界胃肠病学杂志（英文版）

基　　金：Supported by the National Natural Science Foundation of China,No. 30400172, 30230370the National Basic Science and Development programme (973 programme, 2005 CB 522603)

摘　　要：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： Hale 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 （SHA） occlusion. In groups R and A, the rats sustained for 45 min of SHA 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, SHA 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 P21VVAF-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 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 RTPCR 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 P53and 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-1in A group were obviously lower than those in R group at6-12 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

关 键 词：Acid fibroblast growth factor ISCHEMIA REPERFUSION P53 gene P21WAF-1 gene 

分 类 号：R57[医药卫生—消化系统]