四氯化碳诱导大鼠慢性肝损伤的机理及肝脏功能与质量关系的研究.pdfVIP

上海交通大学医学院硕士毕业论文 intravenous injection. Blood was collected from the jugular vein at 5, 10, 20, 30, 45, 60min after drug administration. HPLC assay was established to detect the contents of phenacetin and acetaminophen in plasma. The pharmacokinetic parameters were calculated with PK-Graph software. 2. Determination of CYP1A2 mRNA expression was performed by reverse transcription polymerase chain reaction (RT-PCR); The microsomal content of CYPlA2 was quantitated by Western blotting. Results: 1. The concentration-time curves of phenacetin after intravenous administration in rats fitted one-compartment model. As a result, the AUC of phenacetin was increased by 1.26 times (P 0.01) compared to the control value, and the clearance (CL) of the drug was decreased by 55.7%, T1/2 prolonged. 2. Chronic liver injury significantly increased the plasma concentration of phenacetin at 5min ，10min，20min ，30min，45min points after the iv administration, expecially at 20 and 30min (P 0.01). 3. Significantly low expression of CYP1A2 mRNA was observed in chronic liver injury rats ,approximately 37% the control.(P 0.01). 4. CYP1A2 proteins of chronic liver injury rats were 54.2% of control.(P 0.01). Conclusion: These results indicated that the metabolism of phenacetin is impaired and that CYP1A2 activity is reduced in chronic liver injury rats. The decrease of CYP1A2 activity was due to the reduce of CYP1A2 mRNA, then couse the down regulation of CYP1A2 protein in chronic liver injury rats. Part three Objective: The aim of the study was revealed the relationship between hepatic function and liver mass after defferent liver mass removed in normal rats and chronic liver injury rats . Methods: