姜黄素防止慢性酒精中毒导致的肝损伤

Curcumin can prevent chronic alcohol intoxication induced hepatic injury in rats

目的观察酒精性肝病大鼠肝中核因子κB(nuclearfactorκB,NFκB),单核细胞趋化蛋白1(monocytechemoattractantprotein1,MCP1),巨噬细胞炎症蛋白2(macrophageinflammationprotein2,MIP2)的表达,探讨姜黄素(curcumin)是否能降低酒精性肝病大鼠肝组织中NFκB依赖的基因表达,抑制脂质过氧化(lipidperoxidation)从而防止或减轻酒精性肝损伤(alcoholicliverdisease,ALD)。方法随机将32只SpragueDawley大鼠分成四组(8只/组),乙醇喂养组(E组),乙醇加姜黄素喂养组(EC组),姜黄素加蔗糖喂养组(DC组),蔗糖喂养组(D组),分别在饮水中加入乙醇(50%,vol/vo1)和等热量的蔗糖,姜黄素(75mg·kg-1·d-1)加工进食物中。四组大鼠于12周时测定其血清中ALT,AST浓度及其肝组织中MDA含量,同时用RTPCR测定肝组织中MCP1,MIP2mRNA的表达,用免疫组化方法测定肝组织中NFκB,MCP1的表达,并在光学显微镜下观察肝脏的形态学改变。结果乙醇喂养组中大鼠血清ALT,AST分别为73.7±14.3U/L和154.34±24.6U/L明显高于乙醇加姜黄素组的32.1±11.8U/L和60.3±10.8U/L(P<0.01);乙醇喂养组大鼠肝组织中MDA水平为1.04±0.08nmol/mg也高于乙醇加姜黄素组中的0.51±0.03nmol/mg(P<0.01)。免疫组化结果显示乙醇组大鼠肝组织中有NFκB,MCP1表达。

Objective To determine whether treament with curcumin could suppress the expression of NFκB-dependent genes and prevent ALD.Methods Thirty-two rats were randomly divided into four groups (8rats/group): Rats in the first group were administered ethano l (group E),Rats in the second group were administered dextrose (group D), the third and fourth grou ps of rats received ethanol or dextrose supplemented with 75 mg·kg~)-1(.d~ )-1( curcumin (group EC and group DC).Rats were fed with water supplemented with ethanol (50%,vol/vol) or dextrose. Four groups were treated for 12 weeks before being killed. Levels of alanine transaminase (ALT) and aspartate aminotransferase (AST) in blood were measured, and the expression of MCP-1 and MIP2 mRNA in liver tissues were determined with the reverse transcription polymerase chain reaction(RT-PCR).The expression of MCP-1 and NFκB in the liver tissue we re determined with immunohistochemical analysis.Maloadehyde (MDA) contents in t he liver tissue were measured and histopathological changes were observed in the liver tissues in each group. Results MDA contents in the liver tissue were increased dramatically in ethanol-fed rats(1.0 4±0.08nmol/mg) compared with dextrose-fed rats(0.39±0.02nmol/mg,P<0.01) .Curcumin decreased MDA contents in the group EC )0.51±(0.03nmol/mg,P<0.0 1).Mean values of serum ALT and AST levels were increased significantly in ethanol-fed rats(73.7±14.3U/L and 154.3±24.6U /L),compared with ethanol plus curcumin-fed rats(32.1 4±11.8U/L and 60.3±)10.8U/L,(P<0.01).Immunostaining for NFκB and MCP-1 showed that in tensity of st aining in ethanol-fed rats were strong, degree of staining was decreased in group treated with curcumin.mRNA of MCP-1 and MIP-2 were detected only in ethanol-fed group and not in the othe r groups.In liver sections from ethanol-fed rats, there was marked pathological changes (steatosis,cell infiltration and necrosis).Other groups have normal liv er structure. Conclusions Curcumin can prevent chronic alcohol in toxication induced hepatic injury in rats by inhibiting the expression of NFκB -dependent genes and lipid peroxidation.