Electron Misoscopic Morphology of the Gallbladder and Gallstone Formation induced by High Cholesterol-Cholic Acid Diet in Mice

Han, Nam Ik; Choi, Sang Wook; Lee, Young Sok; Lee, Chang Don; Chung, Kyu Won; Sun, Hee Sik

Abstract

BACKGROUND/AIMS: The experimental production of cholesterol gallstone suggests that alteration of the nature of gallbladder mucus may be a factor in the induction of gallbladder stones. This study was designed to clarify the changes of the gallbladder epithelia and the role of a high cholesterol-cholic acid diet (CCD) in the formation of the gallstones. METHOD: Forty mice were fed on a diet of natural 1% high-cholesterol egg yolk and 2.5% cholic acid for 8 weeks. The mice were sacrificed biweekly and followed up for 8 weeks. The gallbladder tissues and bile were prepared for electron microscopic examination. We observed the ultrastructural changes of the epithelia and the sediments of the gallbladder bile with scanning and transmission electron microscopic observation.
RESULTS
1) Process of Gallstone formation in bile: At the 2nd week in mice fed with CCD, the crystals grew up by appositional layering into monoliths and then by aggregation into mulberry-shaped stones. At the 8th week many stones and numerous concrements were observed. 2) Scanning electron microscopic findings: In mice fed with CCD, the scattered whitish patches of epithelial cell surfaces exhibited the cauliflower-like apical protrusion secreting mucin. These protrusions appeared to be swellings of the apical plasmalemma and they were mixed with the mucus and microvilli. 3) Transmission electron microscope findings: At the 2nd week, numerous electron lucent secretory granules were observed in the apical zone of the epithelial cells. Increased numbers of fat vacuoles were also observed in the basal area of epithelium. Two types of cells were observed in the lining epithelium: dark and light cells.
CONCLUSION
This study suggests that long-term administration of CCD, and the resultant increased secretion of glycoprotein from gallbladder epithelial cells, could be a factor in the induction of the gallstones.