Cellular and molecular mechanisms of 17beta-estradiol postconditioning protection against gastric mucosal injury induced by ischemia/reperfusion in rats.
Life Sciences(2010)
摘要
To investigate the protective effects of 17beta-estradiol postconditioning against ischemia/reperfusion (I-R)-induced gastric mucosal injury in rats.The animal model of gastric ischemia/reperfusion was established by clamping of the celiac artery for 30 min and reperfusion for 30 min, 1h, 3h, 6h, 12h or 24h. 17beta-estradiol at doses of 5, 50 or 100 microg/kg (rat) was administered via peripheral veins 2 min before reperfusion. In a subgroup of rats, the estrogen receptor antagonist fulvestrant (Ful, 2mg/kg) was intravenously injected prior to 17beta-estradiol administration. Histological and immunohistochemical methods were employed to assess the gastric mucosal injury index and gastric mucosal cell apoptosis and proliferation. The malondialdehyde (MDA) concentration, superoxide dismutase (SOD) activity, xanthine oxidase (XOD) activity and hydroxyl free radical (-OH) inhibitory ability were determined by colorimetric assays. Subsequently, the expression of Bcl-2 and Bax in rat gastric mucosa was examined by western blotting.17beta-estradiol dose-dependently inhibited gastric I-R (GI-R) injury, and 17beta-estradiol (50 microg/kg) markedly attenuated GI-R injury 1h after reperfusion. 17beta-estradiol inhibited gastric mucosal cell apoptosis and promoted gastric mucosal cell proliferation in addition to increasing SOD activity and -OH inhibitory ability and decreasing the MDA content and XOD activity. The Bax protein level increased 1h after GI-R and was markedly reduced by intravenous administration of 17beta-estradiol. In contrast, the level of Bcl-2 protein decreased 1h after GI-R and was restored to normal levels by intravenous administration of 17beta-estradiol. These effects of 17beta-estradiol were inhibited by pretreatment with fulvestrant.17beta-estradiol postconditioning should be investigated further as a possible strategy against gastric mucosal injury.
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关键词
17β-estradiol,Gastric ischemia/reperfusion,Apoptosis,Proliferation,Bcl-2,Bax,SOD activity,MDA content,Rat
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