改构型和野生型酸性成纤维细胞生长因子对肠缺血-再灌注损伤的保护作用及剂量-效应关系研究

目的评价改构型和野生型酸性成纤维细胞生长因子(aFGF)对肠缺血-再灌注损伤后肠道保护作用的机制及剂量-效应关系。方法以夹闭大鼠肠系膜上动脉(SMA)制备肠缺血-再灌注损伤模型，并将动物随机分为假手术组、生理盐水对照组、不同剂量(2、4和8μg)改构型aFGF治疗组和4μg野生型aFGF治疗组。除假手术组外，其余各组动物均于缺血45min后再灌注2、6、12和24h活杀，取血及小肠组织标本，检测血浆中D-乳酸含量及组织中增殖细胞核抗原(PCNA)的表达特性，并检测肝、肾功能指标，观察不同剂量aFGF对肠缺血-再灌注损伤的影响。结果血浆D-乳酸变化及病理组织学观察显示，再灌注后12h肠屏障功能及肝、肾组织损伤最严重，而改构型aFGF 4μg治疗组在伤后24h损伤较生理盐水对照组和野生型aFGF治疗组有所减轻。PCNA的表达趋势与D-乳酸类似。结论改构型aFGF对肠缺血-再灌注损伤具有一定保护与促修复作用，其抗损伤修复作用呈剂量依赖性。

Protective effects of acidic fibroblast growth factor on intestinal ischemia/reperfusion in rats

OBJECTIVE: To observe the change in hepatic and renal functions, change in the plasma D-lactate level, and the expression of proliferating cell nuclear antigen (PCNA) after intestinal I/R injury, so as to explore the effects of reconstructive human acid fibroblast growth factor(aFGF) on intestinal I/R injury in rats. METHODS: One hundred and twenty-six Wistar rats were divided into sham-operated, ischemia (45 minutes) plus reperfusion, reconstructive human aFGF treatment (2, 4, 8 microg aFGF) and wild type aFGF(2, 6, 12, and 24 hours, respectively) groups. Hepatic and renal functions and the levels of plasma D-lactate were determined and the expression of PCNA was assessed. RESULTS: Compared with all other groups, bowel barrier function and hepatic and renal functions showed most marked deterioration in sham-operated group. The damages were less marked in reconstructive human aFGF group compared with other groups 24 hours after ischemia/reperfusion of the intestine, and the protective effect was best shown when 4 microg of aFGF was given. The trend of expression of PCNA was similar to that of changes in D-lactate level. CONCLUSION: Wild type reconstructive human aFGF treatment significantly improves the outcome of ischemia/reperfusion injury to the intestine, and the effect is dose-dependent.