Changes of lipid metabolism in plasma, liver and bile during cholesterol gallstone formation in rabbit model

AIM To find out the relationship between the disturbances of lipid metabolism and the formation of cholesterol gallstones by studying the changes of lipid metabolism in plasma, liver tissue and the bile. METHODS Male and female white Japanese rabbits were divided randomly into a control group (Con) and four experimental groups of 10 rabbits each fed with a diet containing 1.2% cholesterol for one, two, three and four weeks (1 wk, 2 wk, 3 wk and 4 wk group). The measurement of plasma triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and its subfractions (HDL2-C, HDL3-C), very low and low density lipoprotein cholesterol (VLDL-C, LDL-C) was taken with standard enzymatic techniques. Apolipoprotein (apo) concentrations in plasma were measured by radial immunodiffusion assay for apoA1, apoB100, aopC II and apoC III. Total cholesterol of liver was measured by the enzymatic procedure for each animal. Bile acids, mainly glycocholate (GCA) and glycodeoxycholate (GDCA) were detected by dual wavelength thin layer scanner. RESULTS In all the experimental groups fed with dietary cholesterol, cholesterol crystal was found in the gallbladder in 2/10 cases of the 1 wk group, 4/10 of the 2 wk group, 6/10 of the 3 wk group and 7/10 of the 4wk group respectively. The concentration of plasma total cholesterol (TC), triglyceride (TG), phospholipid (pl), VLDL-C, LDL-C, apoB100, apoC II, apoC III gradually increased (P<0.05) with the prolonged feeding time of dietary cholesterol. High density lipoprotein cholesterol and its subfractions (HDL-C, HDL2-C, HDL3-C) showed a tendency to decrease, but without statistical significance (P>0.05). ApoA1 was reduced with increased feeding time of dietary cholesterol (P<0.05). The hepatic and biliary cholesterol increased 1-1.5 times as compared with the control group (t=5.221 and 3.445, P<0.05). The GCA gradually decreased beginning from the control group to the 4wk group (P<0.05). CONCLUSION Owing to the high cholesterol diet, the increased concentrations of plasma TC, TG, VLDL-C, LDL-C, hepatic TC and TG, apoB100, apoC II and apoC III possibly enhanced the secretion of biliary cholesterol into bile; the decreased plasma apoA1 level might reduce the secretion of antinucleating factor into bile. All those factors mentioned above probably contribute to the formation of cholesterol gallstones.