中文摘要：

目的:利用内质网应激诱导剂2-脱氧葡萄糖(2-deoxy-D-glucose,2-DG)预处理探究内质网应激对丙烯腈氧化性损伤的保护效应及其作用机制。方法:将36只SD雄性大鼠随机分为6组,即空白组、2-DG组、50 mg/kg丙烯腈组、75 mg/kg丙烯腈组、2-DG+50 mg/kg丙烯腈组、2-DG+75 mg/kg丙烯腈组。采取腹腔注射的方式给予2-DG预处理和急性丙烯腈染毒,空白组注射生理盐水。2-DG预处理为100 mg/kg每天定时腹腔注射1次,持续1周,随后丙烯腈染毒;丙烯腈组腹腔注射丙烯腈(质量浓度为50、75 mg/kg)1 h后麻醉大鼠并断头处死,迅速在冰上分离脑和肝,利用蛋白印迹法检测葡萄糖调节蛋白78(glucose-regulated protein,Grp78)的表达,同时测定肝脏和大脑中丙二醛、还原性谷胱甘肽(GSH)含量和SOD活性。结果:与空白组比较,2-DG对大鼠肝脏和大脑中Grp78的表达具有明显的诱导作用(P【0.05),丙烯腈染毒明显增加大鼠肝脏和大脑中丙二醛含量(P【0.05),但却明显降低GSH含量和SOD活性(P【0.05)。经2-DG预处理后丙烯腈染毒大鼠肝、脑中的丙二醛含量增加幅度减小,且GSH含量和SOD活性的降低也有所缓解。结论:内质网应激诱导能拮抗丙烯腈诱导的氧化性损伤。

英文摘要：

Objective:To explore the effects of pretreatment of endoplasmic reticulum stress on oxidative toxicity of acrylonitrile in rats.Methods:Thirty-six SD rats were randomly divided into six groups as follows:blank control group,2-DG alone treated group,two acrylonitrile treated groups,2-DG pretreated and acrylonitrile treated groups.The animals were intraperitoneally injected daily with 2-DG at the dosage of 100 mg/kg for 1 week,then rats were intraperitoneally injected with acrylonitrile(50,75 mg/kg),and they were decapitated 1 h after the last administration of acrylonitrile or normal saline.The brain and liver tissues were immediately dissected out and weighted on ice.The expression of glucose-regulated protein-78 (Grp78) was determined by Western blotting.Oxidative toxicity of acrylonitrile was assessed by the reduced glutathione levels(GSH),products of lipid peroxidation (MDA),and superoxide dismutase (SOD) activity in the brain and liver.Results:Levels of protein expression of Grp78 increased after pretreatment with 2-DG compared with that of control group(P ＜0.05).A significant increase in levels of MDA was observed in the acrylonitrile-treated group both in the brain and liver compared with the control group(P ＜0.05).These increases were accompanied by a significant decrease in GSH content and a significant reduction in SOD activity in the same tissues (P ＜ 0.05).However,when rats were pretreated with 2-DG,increase of MDA and decrease of GSH contents and SOD activity was significantly attenuated both in liver and brain,compared with acrylonitrile administration alone.Conclusion:Pretreatment with 2-DG reversed the acrylonitrile-induced effects by reducing the levels of MDA and enhancing SOD activity and increasing GSH content both in the brain and liver.