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

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

目的 评价改构型和野生型酸性成纤维细胞生长因子 (a FGF)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 a FGF治疗组和 4 μg野生型 a FGF治疗组。除假手术组外 ,其余各组动物均于缺血 4 5 m in后再灌注 2、6、12和 2 4 h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a FGF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 12 h肠屏障功能及肝、肾组织损伤最严重 ,而改构型 a FGF 4μg治疗组在伤后 2 4 h损伤较生理盐水对照组和野生型 a FGF治疗组有所减轻。PCNA的表达趋势与 D 乳酸类似。结论 改构型 a FGF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。

Objective To observe the change in hepatic and renal functions, change in the plasma Dlactate 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 twentysix Wistar rats were divided into shamoperated, ischemia (45 minutes) plus reperfusion, reconstructive human aFGF treatment (2, 4, 8 μg aFGF) and wild type aFGF(2, 6, 12, and 24 hours, respectively) groups. Hepatic and renal functions and the levels of plasma Dlactate 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 shamoperated 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 μg of aFGF was given. The trend of expression of PCNA was similar to that of changes in Dlactate level. Conclusion Wild type reconstructive human aFGF treatment significantly improves the outcome of ischemia/reperfusion injury to the intestine, and the effect is dosedependent.