摘要
目的探讨槲皮素诱导Ⅰ型血红素氧合酶(heme Oxygenase-1,HO-1)及其代谢产物胆红素对肝细胞酒精性氧化损伤的保护效应。方法二步胶原酶灌注技术分离培养SD大鼠原代肝细胞,在孵以200 mmol乙醇建立酒精性肝细胞氧化损伤模型的同时,加入槲皮素(100μmol)、hemin(20μmol)等及不同剂量(2-100μmol)的胆红素干预24 h后,检测细胞内超氧化物歧化酶(SOD)活力及谷胱甘肽(GSH)、丙二醛(MDA)及氧自由基(ROS)水平及培养基中总胆红素水平。结果槲皮素明显抑制了乙醇孵育后细胞MDA和ROS水平的升高,有效维持了细胞内GSH水平和SOD活力;加入外源性胆红素也显示出相同的保护效应,且具有一定的剂量依赖性;锌原卟啉IX(ZnPP-IX)则明显抑制了上述槲皮素的保护效应。结论槲皮素诱导HO-1对酒精所致大鼠原代肝细胞氧化损伤具有保护作用,其机制与HO-1的代谢产物之一胆红素有关。
Objective To investigate the protective effect of hemeoxygenase-1（HO-1） and its metabolite bilirubin induced by quercetin on ethanol-induced oxidative damage in hepatocytes.Methods Primary hepatocytes were isolated from Sprague-Dawley rat using two-step collagenase perfusion technique.The oxidative damage model was established through ethanol（200 mmol/L） incubation for 24 h.Meanwhile,the ethanol-intoxicated hepatocytes were treated with quercetin（100 μmol/L）,hemin（20 μmol/L） or different dose of bilirubin（2-100 μmol/L）,etc.The activities of superoxide dismutase（SOD）,as well as the levels of malondialdehyde（MDA）,glutathione（GSH）,total bilirubin and reactive oxygen species（ROS） were detected following 24 h incubation.Results Quercetin inhibited the increase of MDA and ROS,the GSH depletion and SOD inactivation in heaptocytes induced by ethanol.Exogenous bilirubin,however,manifested the similar protective effect in dose-dependent manner to some extent.Znpp-IX,HO-1 inhibitor,abolished the protective effect of quercetin.Conclusion Quercetin prevented rat primary hepatocytes from ethnol-induced oxidative damage through the effect of bilirubin,one of the HO-1 metabolites.
出处
《营养学报》
CAS
CSCD
北大核心
2010年第6期528-531,共4页
Acta Nutrimenta Sinica
基金
国家自然科学基金(No.30872117)
教育部新世纪优秀人才支持计划(No.08-0222)
留学回国启动基金(2008)
