NF-κB、Bcl-2与酒精性肝病

NF-κB,Bcl-2 and the alcoholic liver disease

酒精性肝病(ALD)是由于长期过度饮酒而引发的一系列肝脏损害疾病。现研究表明肝细胞的凋亡对该病的发生、发展起着十分重要的作用。其中核因子κB(NF-κB)、B细胞淋巴瘤-2基因(Bcl-2)与ALD关系密切。ALD患者肝细胞内活化的NF-κB,通过刺激大量炎性细胞因子释放,引发肝组织炎症、纤维化、坏死和凋亡,同时通过调控凋亡蛋白酶(Caspase)、Bcl-2、死亡受体等基因来干预肝细胞凋亡;被激活的Bcl-2,除本身具有抗凋亡功能外,还与NF-κB以复合物的形式发挥抗凋亡作用,同时与同家族促凋亡蛋白Bax以二聚体的形式依比例对肝细胞凋亡发挥抑制或促进作用。肝细胞凋亡和抗凋亡的动态失衡将成为酒精性肝病发病的重要途径之一。

Alcoholic liver disease which causes the liver damage is due to the long series of heavy drinking.Present study shows that the hepatocytes apoptosis plays an important role in the development of ALD.The nuclear factor κB（NF-κB） and B cell lymphoma-2 genes（Bcl-2） are closely related with the hepatocyte apoptosis.The activate NF-κB in the hepatocyte of ALD,not only can stimulate the release of inflammatory cytokines and cause liver inflammation,fibrosis,necrosis and apoptosis,but also can interfere the hepatocyte apoptosis by regulation the caspase（Caspase）,Bcl-2,death receptor and other genes.The activated Bcl-2 not only can inhibit apoptosis by itself function,but also can inhibit apoptosis in the form of complex with the activated NF-κB.Bcl-2 can be dimer with the same family protein Bax which is the pro-apoptotic protein.The dimer inhibiting or stimulating apoptosis depends on the proportion of Bcl-2 and Bax.Imbalance of stimulating apoptosis and anti-apoptosis will become an important way in the way of ALD pathogenesy.