雌激素对大鼠肠缺血再灌注损伤的保护作用及对iNOS表达的影响

Protective effect of estrogen on intestinal ischemia-reperfusion injury in pubertal rats and its possible effect on iNOS expression

目的探讨雌激素对肠缺血再灌注损伤(I/R)的保护作用及对诱导型一氧化氮合酶(i-NOS)表达的影响。方法将60只青春期大鼠随机分为4组(每组各15例),假手术组未切除卵巢,其余3组行双侧卵巢切除术,术后隔天分别皮下注射蓖麻油(对照组)、雌二醇(E2,100ug/kg,E2组)、高剂量的E2(500ug/kg,5E2组)4周。将各组大鼠肠系膜上动脉夹闭30min,再灌注时间分别为1h(n=5)、6h(n=5)和24h(n=5)。测血清E2浓度,小肠粘膜行粘膜病理评分、iNOS mRNA表达及iNOS活性测定。结果对照组、假手术组、E2组和5E2组小肠粘膜病理评分分别为3.31±0.12、3.00±0.09、2.57±0.12和2.98±0.08,iNOS mRNA表达水平的拷贝数对数值分别为3.85±0.42、4.86±0.76、5.17±0.34和4.25±0.41。E2组的病理评分低于其它3组(P<0.01),而iNOS mRNA表达水平高于其它3组(P<0.01)。各组iNOS活性水平与iNOS mRNA表达水平一致,E2组iNOS活性高于对照组(P<0.05),亦高于假手术组和5E2组(P值均<0.05)。线性回归分析示血清E2浓度的对数值与病理评分呈负相关(P<0.01)、与iNOS mRNA和iNOS活性呈正相关(P值均<0.01)。结论雌激素对大鼠肠I/R损伤有保护作用,该保护作用与iNOS表达增强有关。

Objective This study investigated the role of 17beta-estradiol （E2） in intestinal is- ehemia-reperfusion （I/R） injury in pubertal rats and its possible effect on iNOS expression. Methods The rats were randomly divided into 4 groups （each group, n = 15）. Rats of pubertal age were ovarieetomized and injected subcutaneously with vehicle （control group） or E2 （100 or 500 mug/kg/every other day, E2 or 5E2 group） for 4 weeks. Other rats of the same age underwent sham ovariectomy as sham-op group. The rats in each group were subjected to 30 minutes occlusion of superior mesenteric artery followed by 1 hour （n=5）, 6 hours （n=5）, or 24 hours （n=5） reperfusion. The blood of rats was obtained for the determination of E2 concentration. Intestine specimens then were harvested for the determination of histopathologic score, mRNA expression of inducible nitric oxide synthase （iNOS）, and iNOS activity. Results In control, sham-op, E2, and 5E2 groups, the histopathologic scores were 3.31 ± 0.12, 3.00 ± 0.09, 2.57 ± 0.12, and 2.98 ± 0.08, respectively. The expression levels of iNOS mRNA were 3.85 ± 0.42, 4.86 ± 0.76, 5.17 ± 0.34, and 4.25 ± 0.41log copies, respectively. Lower histopathologic score but higher iNOS mRNA expression were found in E2 group than in the other groups （P 〈 0.01）. The level of iNOS activity paralleled the expression of iNOS mRNA, A negative lenear correlation was found between the log value of E2 concentration and histopathologic score （P 〈 0.05）. A positive linear correlation was found between the log value of E2 concentration and iNOS mRNA expression （P 〈 0.01）. Conclusions Estrogen may exert a protective effect on intestinal I/R injury in pubertal rats, probably by enhancing iNOS expression.