Xu Guoqiang, Zhao Li, Fuchs Michael
Department of Gastroenterology, First Affiliated Hospital, Medical College of Zhejiang University,79 Qing Chun Road, Hangzhou 310003, China.
Chin Med J (Engl). 2002 Sep;115(9):1292-5.
To investigate differences between hepatic and biliary lipid metabolism and secretion of genetically gallstone-susceptible (C57L) and resistant (AKR) mice and the mechanism of cholesterol gallstone formation.
The inbred C57L and AKR mice were fed a lithogenic diet containing 15% fat, 1.25% cholesterol and 0.5% cholic acid for four weeks. Hepatic cholesterol content and secretion rates of biliary lipids, as well as phenotypes of the liver and gallbladder were determined and examined before and after the feeding of the lithogenic diet.
Both before and after ingestion of the lithogenic diet, hepatic secretion rates of all biliary lipids in C57L mice were markedly higher than that of AKR mice (P < 0.05, P < 0.01, respectively), whereas hepatic cholesterol contents of C57L mice were significantly lower than that of AKR mice (P < 0.05). Furthermore, after consumption of the lithogenic diet, the increase in hepatic secretion rate of biliary cholesterol in C57L mice was significantly higher than that in AKR mice (P < 0.01). Cholesterol gallstones formed in C57L mice and fatty livers developed in AKR mice.
Biliary cholesterol hypersecretion is the key pathophysiological defect of gallstone formation, lith genes have effects on biliary cholesterol hypersecretion and susceptibility to cholesterol gallstone formation in C57L mice. Lithogenic bile is formed at the canalicular membrane and precedes the development of cholesterol gallstones. It is most likely that cholesterol and bile acid hyposecretion make the AKR strain susceptible to the development of fatty livers and resistant to gallstone formation.
研究遗传性胆结石易感（C57L）和抗性（AKR）小鼠肝脏和胆汁脂质代谢及分泌的差异以及胆固醇结石形成的机制。
将近交系C57L和AKR小鼠喂食含15%脂肪、1.25%胆固醇和0.5%胆酸的致石性饮食4周。在喂食致石性饮食前后测定并检查肝脏胆固醇含量、胆汁脂质分泌率以及肝脏和胆囊的表型。
在摄入致石性饮食前后，C57L小鼠所有胆汁脂质的肝脏分泌率均显著高于AKR小鼠（分别为P < 0.05，P < 0.01），而C57L小鼠的肝脏胆固醇含量显著低于AKR小鼠（P < 0.05）。此外，食用致石性饮食后，C57L小鼠胆汁胆固醇肝脏分泌率的增加显著高于AKR小鼠（P < 0.01）。C57L小鼠形成了胆固醇结石，AKR小鼠出现了脂肪肝。
胆汁胆固醇分泌过多是胆结石形成的关键病理生理缺陷，lith基因对C57L小鼠胆汁胆固醇分泌过多及胆固醇结石形成易感性有影响。致石性胆汁在胆小管膜处形成，先于胆固醇结石的形成。很可能胆固醇和胆汁酸分泌不足使AKR品系易患脂肪肝且对结石形成有抗性。
