药物性肝损伤的发病机制（Pathogenesis of drug-induced liver injury）.doc

药物性肝损伤的发病机制（Pathogenesis of drug-induced liver injury） Pathogenesis of drug-induced liver injury 2012-12-12 13:01 source: Chinese Journal of Hepatology, author: Li Zijun et al Font size - | + In 2005, Kaplowitz proposed a concept for the mechanism of drug-induced liver injury (druginducedliver, injury, DILl), namely, upstream events and nonspecific downstream events of drug specific injury. The upstream incident refers to environmental factors and genetic risk factors for initial liver injury caused by; cell damage pathway and cell protection pathway downstream events occur in mitochondria in the balance between. Recently, Russmann proposed the theory of three step mechanism in the pathogenesis of DILI, which is the first drug and its metabolites directly cause cell stress, immune response and inhibition of mitochondrial function in cell activation or organism specificity; then the initial cell damage caused by mitochondrial permeability transition (mitochondrial permeability, transition, MPT); finally, MPT caused liver cell apoptosis or necrosis. However, it is difficult to study the pathogenesis of DILI because of the difficulty of establishing DILI animal model and clinical collection of bulk cases, and the difference between individuals with DILl. DILl is divided into 3 types: hepatocyte necrosis type, cholestasis type and mixed type. The pathogenesis of hepatic necrosis and cholestasis is very different. Genetic factors are the focus of recent studies. 1. Genetic factors responsible for DILI In addition to the individual sex, age, nutritional status, liver basal disease, combined medication and drinking, the relationship between DILI and genetic factors is the most critical factor. Clinically, DILl mostly refers to specific drug-induced liver disease, which occurs only in certain people or populations (specific constitutions), which is related to the genetic background or gene polymorphism of the patients. In recent years, due to the completion of human genome