Changes In Propofol Pharmacokinetics And Extrahepatic UGT1A6 Gene Expression In Anhepatic Rats

Objective: Propofol is an intravenous anesthetic most commonly used in liver transplantation. It is metabolized mainly by the liver and then discharged by the kidneys. Recent studies show that although the metabolism of propofol by the liver is absent in the anhepatic phase during liver transplantation, its metabolism is not affected obviously, suggesting the existence of extrahepatic metabolism and an enhanced extrahepatic metabolism of propofol in the anhepatic phase. But this postulation is to be confirmed. Uridine diphosphate glucuronate transferase 1A6(UGT1A6) may glucuronylate propofol and the product can be directly discharged by the kidney. The liver has the highest contents of UGT1A6 among other tissues and organs. The UGT1A6 expression level is modulated in an immediate, tissue-specific and environment-related manner. In the anhepatic phase of liver transplantation, internal milieu changes drastically, and the levels of some hormones may affect extrahepatic expression of UGT1A6, thus influencing extrahepatic metabolism of propofol. In this study propofol pharmacokinetics in anhepatic rats was studied, and the changes in UGT1A6 gene expression in the kidneys, small intestine, lungs and brain before and after the anhepatic phase were also investigated. And then the changes in serum levels of GH and FT4 before and after the anhepatic phase were analyzed. This study was designed to preliminarily elucidate the mechanisms by which the anhepatic state influences the UGT1A6 expression and the mechanisms of propofol pharmacokinetics in the anhepatic phase.Materials and Methods: This study is composed of three parts: 1.Propofol pharmacokinetic changes in anhepatic rats. The standard curve of rat blood propofol concentration was plotted by high performance liquid chromatograph using standard propofol (1g/ml, purity 99.9%), and the method for measuring propofol concentration using small volumes of blood sample was established. 10 male SPF SD rats were etherized and their right deep cervical vein was incised and inserted with a 1.0 gauge silicone tube. Before and after blocking hepatic hilum, propofol (10 mg/kg) was infused via the right deep...