白藜芦醇诱导HO-1对酒精性肝细胞的保护作用

目的白藜芦醇(resveratrol)是非黄酮类的多酚化合物,具有多种有益的生物学效应。本研究目的观察白藜芦醇对酒精导致的人原代肝细胞损伤的保护作用及机制。方法经体外灌流、分离培养人原代肝细胞。测定白藜芦醇20μmol/L对酒精致肝细胞LDH释放率的影响。人原代肝细胞给予不同受试物(100 mmol/L酒精,20μmol/L白藜芦醇,25μmol/L Znpp9(锌原卟啉Ⅸ:zinc protoporphyrin-IX))24h,观察HO-1酶活性变化,孵育上清液AST,LDH释放水平,肝细胞内MDA,GSH含量变化。结果白藜芦醇可显著升高酒精致肝细胞LDH释放率的EC50(从700 mmol/L上升至1050 mmol/L);白藜芦醇可使肝细胞HO-1酶活性明显增加,并可显著抑制酒精导致的肝细胞AST,LDH释放,降低肝细胞内MDA水平,提高GSH含量。但是HO-1抑制剂Znpp9却明显降低了白藜芦醇对酒精导致的肝细胞损伤的保护作用。结论白藜芦醇对酒精导致的人肝细胞损伤具有保护作用,这种保护作用与其诱导的HO-1酶活性升高有关。

PROTECTION OF RESVERATROL ON UP-REGULATED HO-1 AGAINST ETHANOL-INDUCED HEPATOTOXICITY

Objective To investigate the effects and mechanisms of resveratrol on protection against ethanol-induced human hepatocytes injuries.Method Isolate and culture human primary hepatocytes from human liver tissue after perfusion in vitro,and the effect of resveratrol(20 μmol/L) on LDH releasing rate induced by ethanol was detected.HO-1 activity,AST and LDH in culture supernatants and GSH and MDA of cell lysates were measured in human hepatocytes incubated with ethanol(100 mmol/L),resveratrol(20 μmol/L),Znpp9(25 mmol/L) for 24 h.Results Resveratrol dramatically increased the releasing rate of cellular LDH EC50 by ethanol(from 700 mmol/L to 1050 mmol/L) and enhanced HO-1 activity evidently.Resveratrol apparently exerted protective effect against alcoholic release of AST and LDH,and induced MDA dedepletion,GST elevation.Znpp9,the inhibitor of HO-1,inhibited the resveratrol-related protection.Conclusion Up-regulation of HO-1 activity by resveratrol protected human hepatocytes from ethanol-induced injuries.