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Fatty Liver Disease : Nash and Related Disorders - part 4

Con người và máu các mô của con người, DNA di truyền dễ dàng thu được gan đòi hỏi Số tiền cân nhắc đạo đức bị giới hạn bởi an toàn và hậu cần của kim sinh thiết tế bào văn hóa hạn chế sẵn có-không của khỏe mạnh gan | ANIMAL MODELS OF STEATOHEPATITIS Table 8.1 Why use animal models to study questions about human liver disease Factor Animal model Humans and human tissues Tissue availability Multiple tissues can be sampled Time course easily constructed Liver readily obtained Amount restricted only by animal size Blood genomic DNA readily obtained Liver requires ethical considerations Amount restricted by safety and logistics of needle biopsy Technical approaches Isolated liver cell culture tissue subfractionation all readily available Cell culture restricted by non-availability of healthy liver e.g. excess donor liver Subfractionation requires micromethodology Genetic variation Species differences may thwart interpretation Most relevant species Genetic manipulation Possible especially in mice Complementary approaches loss of function versus gain of function Cross-breeding possible Not possible Selective manipulation of Possible Difficult especially to couple with tissue metabolic pathways Can be coupled with tissue sampling sampling Drug interventions Easy. Can be coupled with tissue sampling Note species differences in pharmacogenetics and pharmacodynamics Ethical safety and logistic issue Hard to couple with tissue sampling Developmental studies Possible Not possible unethical Carcinogenesis studies Possible Rely on opportunistic observations Toxic unethical interventions rats with bile duct ligation develop severe bile acid-mediated oxidative stress acute hepatocellular injury with very high serum alanine aminotransferase ALT levels high mortality depending on strain and development of cirrhosis within 2 months. There are also important physiological differences in eating behaviour including coprophagy and nutritional requirements especially lipid intake and in cytochrome P450 CYP -mediated pathways for hepatic metabolism of fatty acids drugs toxins and carcinogens. Finally it should always be kept in mind that the range of hepatic lesions caused by multiple aetiologies is .