三羟异黄酮对大鼠肠缺血再灌注损伤的保护作用

Protective effects of genistein against intestinal ischemia-reperfusion injury in rats

目的:探讨三羟异黄酮对肠缺血再灌注损伤的保护作用及其机制。方法:24只雄性Wistar大鼠,随机分为3组,每组8只:假手术组、肠缺血再灌注损伤(模型)组和三羟异黄酮组。模型组大鼠肠系膜上动脉被夹闭1 h,然后开放2 h。三羟异黄酮组大鼠在肠缺血前5 min,静脉注射三羟异黄酮1.0 mg.kg-1。假手术组仅暴露肠系膜上动脉。再灌注2 h处死动物取肠标本,观察肠组织病理学变化,测定肠组织湿/干重比(W/D)、髓过氧化物酶(MPO)活性和血浆D-乳酸含量,检测肠组织细胞间粘附分子1(ICAM-1)蛋白表达水平。结果:与假手术组比较,模型组、三羟异黄酮组肠损伤严重,W/D、MPO活性、血浆D-乳酸含量和ICAM-1表达升高(P<0.05或0.01);与模型组比较,三羟异黄酮组肠损伤明显减轻,W/D、MPO活性、血浆D-乳酸含量和ICAM-1表达降低(P<0.05或0.01)。病理学结果显示假手术组肠组织结构正常,模型组损伤严重,三羟异黄酮组轻度损伤。结论:三羟异黄酮对肠缺血再灌注损伤具有保护作用,其机制可能与其下调ICAM-1的表达而抑制中性粒细胞在肠组织的聚集、激活有关。

AIM： To investigate the effects of genistein on intestinal isehemia-reperfusion injury in rats and the possible mechanism. METHODS： Twenty-fourWistar rats were randomly divided into three groups （n=8）： sham operation group, intestinal ischemia-reperfusion injury group（model group） and genistein group. In model group, intestinal damage was induced in rats by clamping the superior mesenteric artery for 1 h, followed by 2 h of reperfusion. Genistein group received genistein 1.0 mg·kg^-1 i.v. 5 min before intestinal ischemia. In genistein group the superior mesenteric artery was o exposured without other treatment. At 2 h of reperfusion, blood samples were collected to measure plasma level of D-lactate and intestines were removed to assay histopathological changes, wet-to-dry weight （W/D） ratio, myelopemxidase （MPO） activity and intercellular adhesion molecule-1 （ ICAM-1 ） protein expression. RESULTS： W/D ratio, MPO activity, expression of ICAM-1 protein in the intestine tissues and D-lactate level in plasma were significantly higher in model and genistein group than those in sham operation group （ P 〈 0.05 or 0.01 ）. All these indices were significantly lower in genistein group than those in model group （ P 〈 0.05 or 0.01 ）. The morphology of lung tissues in sham operation group was basically normal, that in model group was markedly damaged, and that in genistein group was lightly damaged. CONCLUSION： Genistein has protective effect on intestinal ischemia-reperfusion injury in rats. The underlying mechanism may involve an inhibition of neutmphilic recruitment and activity in intestine caused by a down-regulation of ICAM-1 expression.