雌激素对大鼠肠缺血再灌注损伤时TNF-α、ICAM-1表达的影响

Protective effect of estrogen on intestinal ischemia-reperfusion injury in pubertal rats and its possible effect on TNF-α and ICAM-1 expression

目的探讨雌激素对大鼠肠缺血再灌注(I/R)损伤的保护作用以及对肿瘤坏死因子-α(TNF-α)、细胞间黏附因子-1(ICAM-1)表达的影响。方法青春期大鼠随机分为4组(各组n=15),假手术组未切除卵巢,其余3组行双侧卵巢切除术后隔天皮下分别注射蓖麻油(对照组)、雌二醇(E2,E2组)、高剂量的E2(5E2组)4周。各组大鼠行肠系膜上动脉夹闭30min后行再灌注。血清标本测E2浓度,小肠黏膜行黏膜病理评分、TNF-α和I-CAM-1mRNA表达测定。结果对照组、假手术组、E2组和5E2组的血清雌二醇浓度依次增加(各组间P均<0.01)。黏膜病理评分E2组低于其他3组(P<0.01)。组织TNF-α、ICAM-1mRNA表达在E2组最低,对照组最高;E2组的组织TNF-α、ICAM-1mRNA表达比对照组低(P均<0.01)。结论雌激素对大鼠肠I/R损伤有保护作用,该保护作用与抑制TNF-α、ICAM-1表达有关。

Objectives To investigate the role of 17-estradiol （E2） in intestinal ischemia-repeffusion （I/R） injury in pubertal rats and its possible effect on tumor necrosis factor-α （TNF-α） and intercellular adhesion molecule-1 （1CAM-l） expression. Methods The rats were randomly divided into 4 groups in = 15 in each group）. Rats of pubertal age were ovariectomized and injected subcutaneously with vehicle icontrol group） or E2 （100 or 500 μg/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） repeffusion. Blood samples of the rats were taken for measurement of E2 concentration. Intestine specimens were harvested then for the determination of histopathological score, mRNA expression of TNF-α and ICAM-1. Results The serum concentration of E2 were 53.5 ± 20.4, 239.1 ± 41.9, 386.1 ± 95.0, 572.2 ± 147.7 pg/ml in control, sham-op, E2 and 5E2 groups respectively, and with significant difference iP 〈 0.01） between each group. In control, sham-op, E2, and 5E2 groups, the histopathological score were 3.31 ± 0.12, 3.00 ± 0.09, 2.57 ± 0.12, and 2.98 ± 0.08, respectively. Lower histopathological score was found in E2 group than those in the other groups iall P 〈 0.01 ） . The expression levels of TNF-α were 2.67 _± 0.22, 2.56 ± 0.22, 2.38 ± 0.39, 2.63 ± 0.36 log copies, respectively. The expression levels of ICAM-1 paralleled with the expression of TNF-α mRNA, and the log copies were 2.75 ± 0.30, 2.35 ± 0.36, 2.17 ± 0.42, 2.34 ± 0.49, respectively. The expression of TNF-α and ICAM-1 mRNA were found lower in E2 group than that in the control group （P 〈 0.01） . Conclusions Estrogen may exert a protective effect on intestinal I/R injury in pubertal rats, probably by inhibiting the expression of TNF-α and ICAM-1.