| Summary: | 博士 === 國立臺灣大學 === 物理研究所 === 103 === Liver is the largest organ that contains blood, and it is the main organ responsible for maintaining daily function. Since liver is an important organ, therefore, hepatic diseases contributes to a high percentage of mortality rate in whole world. There are millions of people die due to hepatic diseases each year, and the basic causes are injury by acute or chronic hepatic factors. Thus, investigating hepatic diseases is an important subject, with the study of hepatic functions as an important direction to understand the liver. However, in vivo hepatobiliary metabolism remain to be further studied. In this thesis, we used the mouse model and molecular probe 6-carboxyfluorescein diacetate (6-CFDA) to investigate and quantify the hepatobiliary metabolism in normal and diseases livers.
Hepatic acinus is the unit that defined with hepatic functional distribution, there are three defined zones in the hepatic acinus. The three zones are Zone 1, Zone 2, and Zone 3. In this thesis, we setup a first-order mathematic hepatocellular metabolic function to quantify the ratio coefficients of hepatocellular metabolism. In hepatobiliary metabolism, xenobiotic was uptaken from sinusoid into hepatocytes via sinusoidal membrane, and the metabolite was excreted from hepatocytes into bile canaliculi via apical membrane. In these two main processes, the quantification of this two ratio coefficients was defined as k1 and k2 by first-order kinetic function. In normal liver, k1 of Zone 1, 2, and 3 are 0.239, 0.295, and 0.338 (1/min), k2 are 0.0117, 0.0175, and 0.0332 (1/min).
In this thesis, we investigate and quantify the differences and variances in zones of acute hepatic injury and chronic hepatic diseases. In acute liver injury and recovery, the metabolic ratio of Day 4 is the worst and hepatic metabolic function is needed 14 days to be repaired. For chronic hepatic diseases, we focus onto the nonalcoholic fatty liver, hepatic cirrhosis and hepatocellular carcinoma (HCC). For 6-CFDA metabolism, zonal k1 values of fatty liver are 0.179, 0.201, and 0.282 (1/min). The k1 value of three zones are 0.220, 0.229 and 0.2140 (1/min) in liver fibrosis, and 0.372, 0.314 and 0.268 (1/min) in hepatocellular carcinoma. Thus, k2 of fatty liver are 0.0216, 0.0263, and 0.0308 (1/min), k2 of liver fibrosis are 0.0275, 0.0282, and 0.0340 (1/min). Finally, k2 of Zone 1, 2, and 3 are 0.0231, 0.0237, and 0.0283 (1/min) in HCC.
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