细胞色素P450 2E1在酒精性肝损伤中的作用及研究进展

Role and progress of cytochrome P450 2E1 in alcoholic livery injury

酒精性肝病（alcoholic liver disease,ALD）是由各种肝脏细胞和损伤因子（包括氧化应激、亚硝化应激、凋亡诱导因子、内毒素和细胞因子等）相互作用导致的病理生理学病征。肝脏是药物、毒素、合成化合物及氧化产物进行解毒的重要目标器官[1]。

Cytochrome P450 2El （CYP2E1） may be a key pathway in generating oxidative stress, nitrosative stress, lipid peroxidation, and causing alcoholic liver injury by various hepatotoxins. It was found that CYP2E1 induction and liver injury occur with co-administration of ethanol and hepatotoxins. CYP2E1 inducers including alcohol and pyrazole could potentiate the hepatotoxicity caused by FAS antibody or LPS, suggesting that overexpression of CYP2E1 might contribute to the synergy and susceptibility of the liver to FAS/LPS-induced liver injury. Thus, CYP2E1 and its polymorphism have important role in liver injury caused by ethanol and are also associated with nonalcoholic steatohepatitis （NASH）. Ethanol ingestion and toxin administration drive more CYP2E1 induction contributing to the more severe liver injury. Potential mechanisms involved in the potentiated toxicity include elevated oxidative stress, nitrosative stress, lipid peroxidation, apoptosis, hypoxia, TNF-α production, decreased level of antioxidants and activation of MAP kinase. Clarification of CYP2El-dependent liver injury and interactions with other hepatotoxins will lead to a better understanding to the pathogenesis of hepatotoxicity and may help to give strategies which protect the liver from alcoholic liver iniury.