Intravital Imaging of Cellular Dynamics and Microcirculation in Fatty Liver

• Main Authors: Chuang, Shin-Hung, 莊士弘
• Other Authors: Liau, Ian
• Format: Others
• Language: en_US
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/46132834531877263203

碩士 === 國立交通大學 === 應用化學系碩博士班 === 102 === Nonalcoholic fatty liver disease (NAFLD) characterized with an excessive accumulation of fat in the liver tissue has become a prevalent metabolic disease in the developed world. NAFLD could disturb liver function and might progress to fibrosis, cirrhosis and even hepatocellular carcinoma. Past studies have shown that microcirculatory disorder in the sinusoids and activation of leukocytes are associated with NAFLD, our understanding to the role of these phenomena remains incomplete in part due to the lack of tools to decipher these dynamic processes at the microscopic scale in vivo. Herein we employed intravital optical imaging combined with Raman spectral analysis and traditional examinations to interrogate rat models of liver diseases developed to varied severities including mild and severe fatty liver (nonalcoholic steatohepatitis, NASH), and a liver disease characterized with high cholesterol accumulation. Our studies focus on the conditions of hepatic lobules and microcirculation as well as the cells dynamics. The histological and biochemical examination and Raman spectral analysis show that the morphologies of hepatic lobules and lipid profiles differed among these disease models. With intravital imaging, we show that the NASH model exhibits characteristics of inflammation, strong association between leukocytes and platelets, severe lobule injury and impaired microcirculation while other liver disease models present only mild lobule injury. Our preliminary result indicates that the activation of platelets might play an important role in the microcirculatory impairment in NASH. Further mechanistic study is required to elucidate the underlying pathogenesis.