表皮生长因子对大鼠肠缺血-再灌注所致肠黏膜通透性改变的影响

Effect of epidermal growth factor on gut function and mucosal permeability in rats after gut ischemia-reperfusion injury

目的 :观察大鼠肠缺血再灌注后外源性表皮生长因子 (EGF)对肠黏膜通透性和肠、肝、肾功能改变的影响。方法 :80只 3级雄性 Wistar大鼠 ,随机分为假手术 (C)组、肠缺血 (I)组、肠缺血再灌注 (I R)组和EGF治疗组。 I R组和 EGF治疗组均用微血管夹夹闭肠系膜上动脉根部 4 5分钟 ,之后放松血管夹形成再灌注。在再灌注即刻经颈静脉分别注入 EGF 10 0μg/ kg或生理盐水 ,分别于伤后 2、6、12和 2 4小时将动物活杀。C组仅分离肠系膜上动脉根部而不夹闭 ,I组在缺血 4 5分钟后即刻活杀。取血检测肝、肾功能 ,血浆二胺氧化酶(DAO)活性和 D 乳酸浓度 ;取小肠、肝和肾组织进行形态学观察。结果 :1与 C组相比 ,各组动物血浆丙氨酸转氨酶 (AL T)和尿素氮 (BUN)均明显升高 ,但 EGF治疗组升高的幅度显著低于 I R组 (P<0 .0 5 )。2 EGF治疗组的血浆 D 乳酸浓度和 DAO活性在伤后升高的幅度均明显低于 I R组 (P<0 .0 1)。 3EGF治疗组肝、肾和小肠黏膜充血、水肿、炎细胞浸润及局灶性坏死的程度较 I R组显著减轻。结论 :伤后给予外源性 EGF显著减轻了缺血再灌注所致肠、肝、肾功能的损伤 ,其主要作用环节是促进了 EGF与受体的结合及随之发生的信号传导。

Objective:To investigate the effects of exogenous epidermal growth factor(EGF) on gut function and mucosal permeability in rats after gut ischemiareperfusion(IR) insult.Methods:Eighty Wistar rats were randomly divided into four groups,namely EGF treated group(E),normal saline control group(IR), ischemia group(I),sham operated control(C).In group E and IR,the rats were treated with intravenous EGF 100 μg/kg every rat or normal saline respectively after 45 minutes of superior mesenteric artery (SMA) occlusion. Blood samples were collected at 2,6,12 and 24 hours after reperfusion,and organ functional changes were examined.Plasma Dlactate and diamine oxidase (DAO) levels were measured.Tissue samples from intestine, liver and kidney were also taken for histological analysis.Results:SMA occlusion induced tissue damage of intestine,liver and kidneys. In rats treated with EGF and normal saline,the functional parameters of liver and kidneys were markedly changed compared with those in sham operated rats. Intravenous EGF significantly reduced the levels of serum alanine aminotransferase and blood urea nitrogen compared with normal saline controls.The changes of gut histological structure,serum DAO and Dlactate indicated that the intestinal barrier was damaged after intestinal IR injury,while EGF infusion markedly alleviated the damage of intestinal permeability. Conclusions: Exogenous EGF may reduce the functional and histological damage of gut,liver and kidneys in rats induced by IR injury,its main effect might be the improvement to the binding between EGF and its receptor and its subsequent signal transduction.