【作者】 李艳艳； 陈嫚； 禹晓； 徐岩岩； 唐玉涵； 姚平；

【机构】 华中科技大学同济医学院公共卫生学院营养与食品卫生学系；

【摘要】 目的:探讨溶酶体内活性铁在酒精所致肝脏氧化损伤申的作用及槲皮素的拮抗机制。方法:等能量配对喂养雄性C57BL/6J小鼠15周建立酒精继发性铁过载模型。同时灌胃槲皮素及腹腔注射脱铁铵（DFO）进行干预。检测血清转氨酶、肝脏氧化损伤与铁水平相关指标及溶酶体稳定性。乙醇（100 mmol/L）孵育经FeCl₃、DFO及槲皮素干预后小鼠原代肝细胞24小时。测定溶酶体内活性铁含量并分析肝细胞的损伤水平。结果:与正常对照组相比,长期酒精喂养明显引起小鼠肝脏氧化损伤,同时肝脏总铁含量、可变铁池（LIP）水平、溶酶体內活性铁水平、铁蛋白轻链（Ft-L）及瞬时受体潜在粘脂蛋白（TRPML1）表达显著升高,而溶酶体膜稳定性显著降低。槲皮素干预有效改善酒精引起的肝脏铁过载与氧化损伤,并不同程度的降低酒精所致Ft-L、TRPML1的异常高表达,提高溶酶体膜稳定性。减少溶酶体内铁减轻酒精引起的肝细胞氧化损伤而增加溶酶体内铁加重这种损伤。结论:溶酶体内活性铁在酒精性肝损伤中发挥重要的作用,槲皮素通过降低溶酶体內活性铁减轻酒精引起的肝脏氧化损伤。更多还原

【Abstract】 Objectives:To investigate the role of lysosome redox active iron toxicity in ethanol-induced liver oxidative damage and the protective effects of quercetin.Methods;The male C57BL/6J mice were pair-fed with either regular or ethanol-conlaining Iieber De Carli liquids diets for 15 weeks.At the same time,quercetin and DFO were received by gavage and mtrapentoneal injections respectively according to the body weight.The leakage of transaminases,together with hepatic redox and iron-related parameters,and lysosomal damage were assayed.Results;Compared with normal control,intracellular iron,hepatic LIP and intralysosomal iron were significantly increased in ethanol—exposed mice liver,accompanying the sustained oxidative damage.The hepatotoxicity was relieved by reducing lysosomal iron while aggravated by escalating lysosomal iron.Quercetin substantially alleviated the lysosomal iron- mediated alcoholic liver injury by normalizing ethanol stimulated the increase of ferritin light chain(Ft-L) and the typr IV mucolipidosis- associated protein(TRPML1) expression and extenuating lysosomal membrane permeabilization(LMP).Conclusion;Lysosomal redox-active iron played a major role in ethanol elicited liver oxidative damage,quercetin exhibits powerful protection against alcoholic liver damage by lowering intralysosomal redox-active iron pool and consequent the mitigation of lysosome damage.更多还原