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

Abstract

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 (1wk, 2wk, 3wk and 4wk group). The measurement of plasma triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and its subfractions (HDL(2)-C, HDL(3)-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, aopCII and apoC . 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 1wk group, 4/10 of the 2wk group,6/10 of the 3wk 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, apoCII, apoC gradually increased (P < 0.05)with the prolonged feeding time of dietary cholesterol. High density lipoprotein cholesterol and its subfractions (HDL(2)-C, HDL(3)-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, apoCII and apoC 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.