酸性成纤维细胞生长因子对大鼠缺血/再灌注损伤肠上皮细胞丝裂素活化蛋白激酶的影响

目的 观察外源性酸性成纤维细胞生长因子（aFGF）对大鼠缺血／再灌注（I／R）损伤后肠上皮细胞丝裂素活化蛋白激酶（MAPK）活性的影响，并探讨其与肠上皮细胞增殖能力变化的关系。方法 采用大鼠肠系膜上动脉夹闭法制备缺血45min后再灌注动物模型。132只Wistar大鼠随机分为假手术组、I／R组、aFGF处理组（再灌注即刻颈静脉注射aFGF 4μg）及细胞外信号调节蛋白激酶（ERK1／2）阻断剂PD98059预处理组（缺血前尾静脉注射PD98059 7．5μg，再灌注即刻静脉注射aFGF 4μg）。检测缺血前，I／R15、30min及1、2、6、12和24h时肠上皮细胞增殖能力和MAPK活性。结果 aFGF处理后肠上皮细胞增殖明显增加，同时MAPK活性显著增高。用p44／p42MAPK（ERK1／2）阻断剂PD98059可抑制ERK1／2的活性，使肠上皮细胞增殖减少。结论 aFGF可促进I／R损伤后肠上皮细胞增殖，并可能与其激活肠上皮MAPK有关。

Effect of acidic fibroblast growth factor on mitogen-activated protein kinase activity in small intestinal epithelium after ischemia/reperfusion injury in rat

OBJECTIVE: To investigate the effect of acidic fibroblast growth factor (aFGF) on p44/p42 mitogen-activated protein kinase (p44/p42 MAPK, extracellular signal-regulated protein kinase, ERK1/2) activity in small intestinal epithelium in rat after ischemia/reperfusion (I/R) injury and its relation with the change in small intestinal epithelium in rat after I/R injury as well as the change in proliferation of epithelial cells. METHODS: Superior mesenteric artery (SMA) was occluded to produce ischemia of the intestine for 45 minutes followed by reperfusion to reproduce I/R injury. One hundred and thirty-two Wistar rats were randomly divided into sham-operation group, I/R group, aFGF treatment group (4 microg of aFGF was injected into jugular vein after reperfusion), and PD98059 (antagonist of ERK 1/2) pretreatment group (7.5 microg of PD98059 was injected via tail vein before ischemia and 4 microg of aFGF was injected via jugular vein after reperfusion). The activity of ERK1/2 and proliferation rate of small intestinal epithelial cells were determined before ischemia and 15 minutes, 30 minutes, 1 hour, 2 hours, 6 hours, 12 hours and 24 hours after reperfusion. RESULTS: The activity of ERK1/2 in small intestinal epithelium was higher in aFGF treatment group than in I/R control group, and the proliferation rate in small intestinal epithelial cells was significantly enhanced in aFGF treatment group. PD98059, the specific inhibitor of ERK1/2, inhibited ERK1/2 activity and reduced the proliferation rate of small intestinal epithelial cells in aFGF treatment group. CONCLUSION: aFGF can promote small intestinal epithelial cell proliferation in I/R injury rats, and this may be related to activation of ERK1/2 in small intestinal epithelium.